Antibody data
- Antibody Data
- Antigen structure
- References [78]
- Comments [0]
- Validations
- Other assay [28]
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- Product number
- 14-0048-80 - Provider product page
- Provider
- Invitrogen Antibodies
- Product name
- CD4 Monoclonal Antibody (OKT4 (OKT-4)), eBioscience™
- Antibody type
- Monoclonal
- Antigen
- Other
- Description
- Description: The OKT4 monoclonal antibody reacts with human CD4, a 59 kDa cell surface glycoprotein expressed by the majority of thymocytes, a subpopulation of mature T cells (T-helper cells) and in low levels on monocytes. CD4 is a receptor for the human immunodeficiency virus (HIV). The OKT4 antibody recognizes a different epitope than the RPA-T4 monoclonal antibody, and these antibodies do not cross-block binding to each other's respective epitopes.
- Antibody clone number
- OKT4 (OKT-4)
- Concentration
- 0.5 mg/mL
Submitted references Plasma Extracellular Vesicle Subtypes May be Useful as Potential Biomarkers of Immune Activation in People With HIV.
Targeting Phosphatidylserine Enhances the Anti-tumor Response to Tumor-Directed Radiation Therapy in a Preclinical Model of Melanoma.
A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity.
The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses.
Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody.
Antibody-Dependent Cellular Cytotoxicity (ADCC)-Mediating Antibodies Constrain Neutralizing Antibody Escape Pathway.
CD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-Induced Antibodies.
Deep single-cell RNA sequencing data of individual T cells from treatment-naïve colorectal cancer patients.
Calnexin Impairs the Antitumor Immunity of CD4(+) and CD8(+) T Cells.
Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab.
Immune Checkpoint Inhibitor-induced Reinvigoration of Tumor-infiltrating CD8(+) T Cells is Determined by Their Differentiation Status in Glioblastoma.
An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.
The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells.
Complement receptor CD46 co-stimulates optimal human CD8(+) T cell effector function via fatty acid metabolism.
A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells.
Accumulation of T-helper 22 cells, interleukin-22 and myeloid-derived suppressor cells promotes gastric cancer progression in elderly patients.
IL-6 receptor blockade corrects defects of XIAP-deficient regulatory T cells.
Targeted Disruption of TCF12 Reveals HEB as Essential in Human Mesodermal Specification and Hematopoiesis.
Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing.
Ex vivo culture of human atherosclerotic plaques: A model to study immune cells in atherogenesis.
Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice.
Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.
Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo.
Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.
Tax and Semaphorin 4D Released from Lymphocytes Infected with Human Lymphotropic Virus Type 1 and Their Effect on Neurite Growth.
Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity.
Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.
PD-L1 expression and prognostic impact in glioblastoma.
Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets.
Higher Frequency of NK and CD4+ T-Cells in Mucosa and Potent Cytotoxic Response in HIV Controllers.
T lymphocyte density and distribution in human colorectal mucosa, and inefficiency of current cell isolation protocols.
The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.
Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation.
A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity.
The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals.
SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling.
Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients.
An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma.
High avidity CD8+ T cells efficiently eliminate motile HIV-infected targets and execute a locally focused program of anti-viral function.
CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.
CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.
Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans.
Signal transduction by different forms of the γδ T cell-specific pattern recognition receptor WC1.
The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques.
The antiangiogenic insulin receptor substrate-1 antisense oligonucleotide aganirsen impairs AU-rich mRNA stability by reducing 14-3-3β-tristetraprolin protein complex, reducing inflammation and psoriatic lesion size in patients.
HIV-1 autologous antibody neutralization associates with mother to child transmission.
Increased soluble CD4 in serum of rheumatoid arthritis patients is generated by matrix metalloproteinase (MMP)-like proteinases.
Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.
B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients.
CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses.
Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques.
Somatostatin expression in human hair follicles and its potential role in immune privilege.
CD40L expression permits CD8+ T cells to execute immunologic helper functions.
Phosphoantigen/IL2 expansion and differentiation of Vγ2Vδ2 T cells increase resistance to tuberculosis in nonhuman primates.
Novel serial positive enrichment technology enables clinical multiparameter cell sorting.
Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.
Engagement of T-cell antigen receptor and CD4/CD8 co-receptors induces prolonged STAT activation through autocrine/paracrine stimulation in human primary T cells.
Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques.
An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors.
CD4-like immunological function by CD4- T cells in multiple natural hosts of simian immunodeficiency virus.
C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif.
Significant mobilization of both conventional and regulatory T cells with AMD3100.
Direct antibody access to the HIV-1 membrane-proximal external region positively correlates with neutralization sensitivity.
An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching.
The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum.
Novel role of plasmacytoid dendritic cells in humans: induction of interleukin-10-producing Treg cells by plasmacytoid dendritic cells in patients with rheumatoid arthritis responding to therapy.
DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas.
Multicolor flow cytometry analyses of cellular immune response in rhesus macaques.
Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor.
Gammadelta T cell immune manipulation during chronic phase of simian-human immunodeficiency virus infection [corrected] confers immunological benefits.
A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation.
CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface.
Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease.
The Mi-2/NuRD complex associates with pericentromeric heterochromatin during S phase in rapidly proliferating lymphoid cells.
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.
The Ixodes scapularis salivary protein, salp15, prevents the association of HIV-1 gp120 and CD4.
Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1.
Separation of functional subsets of human T cells by a monoclonal antibody.
Bazié WW, Boucher J, Vitry J, Goyer B, Routy JP, Tremblay C, Trottier S, Jenabian MA, Provost P, Alary M, Gilbert C
Pathogens & immunity 2021;6(1):1-28
Pathogens & immunity 2021;6(1):1-28
Targeting Phosphatidylserine Enhances the Anti-tumor Response to Tumor-Directed Radiation Therapy in a Preclinical Model of Melanoma.
Budhu S, Giese R, Gupta A, Fitzgerald K, Zappasodi R, Schad S, Hirschhorn D, Campesato LF, De Henau O, Gigoux M, Liu C, Mazo G, Deng L, Barker CA, Wolchok JD, Merghoub T
Cell reports 2021 Jan 12;34(2):108620
Cell reports 2021 Jan 12;34(2):108620
A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity.
Hammill JA, Kwiecien JM, Dvorkin-Gheva A, Lau VWC, Baker C, Wu Y, Bezverbnaya K, Aarts C, Heslen CW, Denisova GF, Derocher H, Milne K, Nelson BH, Bramson JL
Molecular therapy oncolytics 2020 Jun 26;17:278-292
Molecular therapy oncolytics 2020 Jun 26;17:278-292
The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses.
Beltrán Hernández I, Angelier ML, Del Buono D'Ondes T, Di Maggio A, Yu Y, Oliveira S
Cancers 2020 Apr 15;12(4)
Cancers 2020 Apr 15;12(4)
Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody.
Dao T, Mun SS, Scott AC, Jarvis CA, Korontsvit T, Yang Z, Liu L, Klatt MG, Guerreiro M, Selvakumar A, Brea EJ, Oh C, Liu C, Scheinberg DA
Oncoimmunology 2019;8(7):1570778
Oncoimmunology 2019;8(7):1570778
Antibody-Dependent Cellular Cytotoxicity (ADCC)-Mediating Antibodies Constrain Neutralizing Antibody Escape Pathway.
Mielke D, Bandawe G, Pollara J, Abrahams MR, Nyanhete T, Moore PL, Thebus R, Yates NL, Kappes JC, Ochsenbauer C, Garrett N, Abdool Karim S, Tomaras GD, Montefiori D, Morris L, Ferrari G, Williamson C
Frontiers in immunology 2019;10:2875
Frontiers in immunology 2019;10:2875
CD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-Induced Antibodies.
Ding S, Gasser R, Gendron-Lepage G, Medjahed H, Tolbert WD, Sodroski J, Pazgier M, Finzi A
Journal of virology 2019 Nov 15;93(22)
Journal of virology 2019 Nov 15;93(22)
Deep single-cell RNA sequencing data of individual T cells from treatment-naïve colorectal cancer patients.
Zhang Y, Zheng L, Zhang L, Hu X, Ren X, Zhang Z
Scientific data 2019 Jul 24;6(1):131
Scientific data 2019 Jul 24;6(1):131
Calnexin Impairs the Antitumor Immunity of CD4(+) and CD8(+) T Cells.
Chen Y, Ma D, Wang X, Fang J, Liu X, Song J, Li X, Ren X, Li Q, Li Q, Wen S, Luo L, Xia J, Cui J, Zeng G, Chen L, Cheng B, Wang Z
Cancer immunology research 2019 Jan;7(1):123-135
Cancer immunology research 2019 Jan;7(1):123-135
Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab.
Serra-Peinado C, Grau-Expósito J, Luque-Ballesteros L, Astorga-Gamaza A, Navarro J, Gallego-Rodriguez J, Martin M, Curran A, Burgos J, Ribera E, Raventós B, Willekens R, Torrella A, Planas B, Badía R, Garcia F, Castellví J, Genescà M, Falcó V, Buzon MJ
Nature communications 2019 Aug 16;10(1):3705
Nature communications 2019 Aug 16;10(1):3705
Immune Checkpoint Inhibitor-induced Reinvigoration of Tumor-infiltrating CD8(+) T Cells is Determined by Their Differentiation Status in Glioblastoma.
Park J, Kwon M, Kim KH, Kim TS, Hong SH, Kim CG, Kang SG, Moon JH, Kim EH, Park SH, Chang JH, Shin EC
Clinical cancer research : an official journal of the American Association for Cancer Research 2019 Apr 15;25(8):2549-2559
Clinical cancer research : an official journal of the American Association for Cancer Research 2019 Apr 15;25(8):2549-2559
An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.
Alsahafi N, Bakouche N, Kazemi M, Richard J, Ding S, Bhattacharyya S, Das D, Anand SP, Prévost J, Tolbert WD, Lu H, Medjahed H, Gendron-Lepage G, Ortega Delgado GG, Kirk S, Melillo B, Mothes W, Sodroski J, Smith AB 3rd, Kaufmann DE, Wu X, Pazgier M, Rouiller I, Finzi A, Munro JB
Cell host & microbe 2019 Apr 10;25(4):578-587.e5
Cell host & microbe 2019 Apr 10;25(4):578-587.e5
The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells.
Wallin EF, Hill DL, Linterman MA, Wood KJ
Frontiers in immunology 2018;9:1184
Frontiers in immunology 2018;9:1184
Complement receptor CD46 co-stimulates optimal human CD8(+) T cell effector function via fatty acid metabolism.
Arbore G, West EE, Rahman J, Le Friec G, Niyonzima N, Pirooznia M, Tunc I, Pavlidis P, Powell N, Li Y, Liu P, Servais A, Couzi L, Fremeaux-Bacchi V, Placais L, Ferraro A, Walsh PR, Kavanagh D, Afzali B, Lavender P, Lachmann HJ, Kemper C
Nature communications 2018 Oct 10;9(1):4186
Nature communications 2018 Oct 10;9(1):4186
A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells.
Brey CU, Proff J, Teufert N, Salzer B, Brozy J, Münz M, Pendzialek J, Ensser A, Holter W, Lehner M
Scientific reports 2018 Nov 28;8(1):17453
Scientific reports 2018 Nov 28;8(1):17453
Accumulation of T-helper 22 cells, interleukin-22 and myeloid-derived suppressor cells promotes gastric cancer progression in elderly patients.
Chen X, Wang Y, Wang J, Wen J, Jia X, Wang X, Zhang H
Oncology letters 2018 Jul;16(1):253-261
Oncology letters 2018 Jul;16(1):253-261
IL-6 receptor blockade corrects defects of XIAP-deficient regulatory T cells.
Hsieh WC, Hsu TS, Chang YJ, Lai MZ
Nature communications 2018 Jan 31;9(1):463
Nature communications 2018 Jan 31;9(1):463
Targeted Disruption of TCF12 Reveals HEB as Essential in Human Mesodermal Specification and Hematopoiesis.
Li Y, Brauer PM, Singh J, Xhiku S, Yoganathan K, Zúñiga-Pflücker JC, Anderson MK
Stem cell reports 2017 Sep 12;9(3):779-795
Stem cell reports 2017 Sep 12;9(3):779-795
Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing.
Guzzo C, Ichikawa D, Park C, Phillips D, Liu Q, Zhang P, Kwon A, Miao H, Lu J, Rehm C, Arthos J, Cicala C, Cohen MS, Fauci AS, Kehrl JH, Lusso P
Science immunology 2017 May 12;2(11)
Science immunology 2017 May 12;2(11)
Ex vivo culture of human atherosclerotic plaques: A model to study immune cells in atherogenesis.
Lebedeva A, Vorobyeva D, Vagida M, Ivanova O, Felker E, Fitzgerald W, Danilova N, Gontarenko V, Shpektor A, Vasilieva E, Margolis L
Atherosclerosis 2017 Dec;267:90-98
Atherosclerosis 2017 Dec;267:90-98
Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice.
Dimitrov V, Bouttier M, Boukhaled G, Salehi-Tabar R, Avramescu RG, Memari B, Hasaj B, Lukacs GL, Krawczyk CM, White JH
The Journal of biological chemistry 2017 Dec 15;292(50):20657-20668
The Journal of biological chemistry 2017 Dec 15;292(50):20657-20668
Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.
Tischner D, Grimm M, Kaur H, Staudenraus D, Carvalho J, Looso M, Günther S, Wanke F, Moos S, Siller N, Breuer J, Schwab N, Zipp F, Waisman A, Kurschus FC, Offermanns S, Wettschureck N
JCI insight 2017 Aug 3;2(15)
JCI insight 2017 Aug 3;2(15)
Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo.
Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AAK, Lorenzi JCC, Nogueira L, Golijanin J, Scheid JF, Seaman MS, Gazumyan A, Zolla-Pazner S, Nussenzweig MC
Cell 2017 Aug 10;170(4):637-648.e10
Cell 2017 Aug 10;170(4):637-648.e10
Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.
Boardman DA, Philippeos C, Fruhwirth GO, Ibrahim MA, Hannen RF, Cooper D, Marelli-Berg FM, Watt FM, Lechler RI, Maher J, Smyth LA, Lombardi G
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2017 Apr;17(4):931-943
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2017 Apr;17(4):931-943
Tax and Semaphorin 4D Released from Lymphocytes Infected with Human Lymphotropic Virus Type 1 and Their Effect on Neurite Growth.
Quintremil S, Alberti C, Rivera M, Medina F, Puente J, Cartier L, Ramírez E, Tanaka Y, Valenzuela MA
AIDS research and human retroviruses 2016 Jan;32(1):68-79
AIDS research and human retroviruses 2016 Jan;32(1):68-79
Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity.
Richard J, Veillette M, Ding S, Zoubchenok D, Alsahafi N, Coutu M, Brassard N, Park J, Courter JR, Melillo B, Smith AB 3rd, Shaw GM, Hahn BH, Sodroski J, Kaufmann DE, Finzi A
EBioMedicine 2016 Jan;3:122-134
EBioMedicine 2016 Jan;3:122-134
Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.
Lin YC, Winokur P, Blake A, Wu T, Manischewitz J, King LR, Romm E, Golding H, Bielekova B
Neurology(R) neuroimmunology & neuroinflammation 2016 Feb;3(1):e196
Neurology(R) neuroimmunology & neuroinflammation 2016 Feb;3(1):e196
PD-L1 expression and prognostic impact in glioblastoma.
Nduom EK, Wei J, Yaghi NK, Huang N, Kong LY, Gabrusiewicz K, Ling X, Zhou S, Ivan C, Chen JQ, Burks JK, Fuller GN, Calin GA, Conrad CA, Creasy C, Ritthipichai K, Radvanyi L, Heimberger AB
Neuro-oncology 2016 Feb;18(2):195-205
Neuro-oncology 2016 Feb;18(2):195-205
Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets.
Muller L, Mitsuhashi M, Simms P, Gooding WE, Whiteside TL
Scientific reports 2016 Feb 4;6:20254
Scientific reports 2016 Feb 4;6:20254
Higher Frequency of NK and CD4+ T-Cells in Mucosa and Potent Cytotoxic Response in HIV Controllers.
Taborda NA, González SM, Alvarez CM, Correa LA, Montoya CJ, Rugeles MT
PloS one 2015;10(8):e0136292
PloS one 2015;10(8):e0136292
T lymphocyte density and distribution in human colorectal mucosa, and inefficiency of current cell isolation protocols.
Preza GC, Yang OO, Elliott J, Anton PA, Ochoa MT
PloS one 2015;10(4):e0122723
PloS one 2015;10(4):e0122723
The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.
Goodfellow HS, Frushicheva MP, Ji Q, Cheng DA, Kadlecek TA, Cantor AJ, Kuriyan J, Chakraborty AK, Salomon A, Weiss A
Science signaling 2015 May 19;8(377):ra49
Science signaling 2015 May 19;8(377):ra49
Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation.
Ji Q, Salomon AR
Journal of proteome research 2015 May 1;14(5):2082-9
Journal of proteome research 2015 May 1;14(5):2082-9
A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity.
Garcia-Perez J, Staropoli I, Azoulay S, Heinrich JT, Cascajero A, Colin P, Lortat-Jacob H, Arenzana-Seisdedos F, Alcami J, Kellenberger E, Lagane B
Retrovirology 2015 Jun 18;12:50
Retrovirology 2015 Jun 18;12:50
The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals.
Veillette M, Coutu M, Richard J, Batraville LA, Dagher O, Bernard N, Tremblay C, Kaufmann DE, Roger M, Finzi A
Journal of virology 2015 Jan;89(1):545-51
Journal of virology 2015 Jan;89(1):545-51
SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling.
Ji Q, Ding Y, Salomon AR
Molecular & cellular proteomics : MCP 2015 Jan;14(1):30-40
Molecular & cellular proteomics : MCP 2015 Jan;14(1):30-40
Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients.
Magalhaes I, Pingris K, Poitou C, Bessoles S, Venteclef N, Kiaf B, Beaudoin L, Da Silva J, Allatif O, Rossjohn J, Kjer-Nielsen L, McCluskey J, Ledoux S, Genser L, Torcivia A, Soudais C, Lantz O, Boitard C, Aron-Wisnewsky J, Larger E, Clément K, Lehuen A
The Journal of clinical investigation 2015 Apr;125(4):1752-62
The Journal of clinical investigation 2015 Apr;125(4):1752-62
An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma.
Tang Y, Xu X, Guo S, Zhang C, Tang Y, Tian Y, Ni B, Lu B, Wang H
PloS one 2014;9(3):e91551
PloS one 2014;9(3):e91551
High avidity CD8+ T cells efficiently eliminate motile HIV-infected targets and execute a locally focused program of anti-viral function.
Foley MH, Forcier T, McAndrew E, Gonzalez M, Chen H, Juelg B, Walker BD, Irvine DJ
PloS one 2014;9(2):e87873
PloS one 2014;9(2):e87873
CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.
Zhen A, Krutzik SR, Levin BR, Kasparian S, Zack JA, Kitchen SG
Journal of virology 2014 Sep 1;88(17):9934-46
Journal of virology 2014 Sep 1;88(17):9934-46
CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.
Martínez-Muñoz L, Barroso R, Dyrhaug SY, Navarro G, Lucas P, Soriano SF, Vega B, Costas C, Muñoz-Fernández MÁ, Santiago C, Rodríguez Frade JM, Franco R, Mellado M
Proceedings of the National Academy of Sciences of the United States of America 2014 May 13;111(19):E1960-9
Proceedings of the National Academy of Sciences of the United States of America 2014 May 13;111(19):E1960-9
Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans.
Wertheimer AM, Bennett MS, Park B, Uhrlaub JL, Martinez C, Pulko V, Currier NL, Nikolich-Žugich D, Kaye J, Nikolich-Žugich J
Journal of immunology (Baltimore, Md. : 1950) 2014 Mar 1;192(5):2143-55
Journal of immunology (Baltimore, Md. : 1950) 2014 Mar 1;192(5):2143-55
Signal transduction by different forms of the γδ T cell-specific pattern recognition receptor WC1.
Chen C, Hsu H, Hudgens E, Telfer JC, Baldwin CL
Journal of immunology (Baltimore, Md. : 1950) 2014 Jul 1;193(1):379-90
Journal of immunology (Baltimore, Md. : 1950) 2014 Jul 1;193(1):379-90
The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques.
McGee K, Haim H, Korioth-Schmitz B, Espy N, Javanbakht H, Letvin N, Sodroski J
Journal of virology 2014 Jan;88(1):21-40
Journal of virology 2014 Jan;88(1):21-40
The antiangiogenic insulin receptor substrate-1 antisense oligonucleotide aganirsen impairs AU-rich mRNA stability by reducing 14-3-3β-tristetraprolin protein complex, reducing inflammation and psoriatic lesion size in patients.
Colin S, Darné B, Kadi A, Ferry A, Favier M, Lesaffre C, Conduzorgues JP, Al-Mahmood S, Doss N
The Journal of pharmacology and experimental therapeutics 2014 Apr;349(1):107-17
The Journal of pharmacology and experimental therapeutics 2014 Apr;349(1):107-17
HIV-1 autologous antibody neutralization associates with mother to child transmission.
Baan E, de Ronde A, Stax M, Sanders RW, Luchters S, Vyankandondera J, Lange JM, Pollakis G, Paxton WA
PloS one 2013;8(7):e69274
PloS one 2013;8(7):e69274
Increased soluble CD4 in serum of rheumatoid arthritis patients is generated by matrix metalloproteinase (MMP)-like proteinases.
Tseng WY, Huang YS, Chiang NY, Chou YP, Wu YJ, Luo SF, Kuo CF, Lin KM, Lin HH
PloS one 2013;8(5):e63963
PloS one 2013;8(5):e63963
Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.
Sena A, Grishina I, Thai A, Goulart L, Macal M, Fenton A, Li J, Prindiville T, Oliani SM, Dandekar S, Goulart L, Sankaran-Walters S
PloS one 2013;8(10):e76969
PloS one 2013;8(10):e76969
B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients.
Shubin NJ, Monaghan SF, Heffernan DS, Chung CS, Ayala A
Critical care (London, England) 2013 Nov 29;17(6):R276
Critical care (London, England) 2013 Nov 29;17(6):R276
CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses.
Harfuddin Z, Kwajah S, Chong Nyi Sim A, Macary PA, Schwarz H
Oncoimmunology 2013 Nov 1;2(11):e26859
Oncoimmunology 2013 Nov 1;2(11):e26859
Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques.
Canary LA, Vinton CL, Morcock DR, Pierce JB, Estes JD, Brenchley JM, Klatt NR
Journal of immunology (Baltimore, Md. : 1950) 2013 Mar 15;190(6):2959-65
Journal of immunology (Baltimore, Md. : 1950) 2013 Mar 15;190(6):2959-65
Somatostatin expression in human hair follicles and its potential role in immune privilege.
Breitkopf T, Lo BK, Leung G, Wang E, Yu M, Carr N, Zloty D, Cowan B, Shapiro J, McElwee KJ
The Journal of investigative dermatology 2013 Jul;133(7):1722-30
The Journal of investigative dermatology 2013 Jul;133(7):1722-30
CD40L expression permits CD8+ T cells to execute immunologic helper functions.
Frentsch M, Stark R, Matzmohr N, Meier S, Durlanik S, Schulz AR, Stervbo U, Jürchott K, Gebhardt F, Heine G, Reuter MA, Betts MR, Busch D, Thiel A
Blood 2013 Jul 18;122(3):405-12
Blood 2013 Jul 18;122(3):405-12
Phosphoantigen/IL2 expansion and differentiation of Vγ2Vδ2 T cells increase resistance to tuberculosis in nonhuman primates.
Chen CY, Yao S, Huang D, Wei H, Sicard H, Zeng G, Jomaa H, Larsen MH, Jacobs WR Jr, Wang R, Letvin N, Shen Y, Qiu L, Shen L, Chen ZW
PLoS pathogens 2013 Aug;9(8):e1003501
PLoS pathogens 2013 Aug;9(8):e1003501
Novel serial positive enrichment technology enables clinical multiparameter cell sorting.
Stemberger C, Dreher S, Tschulik C, Piossek C, Bet J, Yamamoto TN, Schiemann M, Neuenhahn M, Martin K, Schlapschy M, Skerra A, Schmidt T, Edinger M, Riddell SR, Germeroth L, Busch DH
PloS one 2012;7(4):e35798
PloS one 2012;7(4):e35798
Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.
Cao L, Ding Y, Hung N, Yu K, Ritz A, Raphael BJ, Salomon AR
PloS one 2012;7(10):e46725
PloS one 2012;7(10):e46725
Engagement of T-cell antigen receptor and CD4/CD8 co-receptors induces prolonged STAT activation through autocrine/paracrine stimulation in human primary T cells.
Chueh FY, Yu CL
Biochemical and biophysical research communications 2012 Sep 21;426(2):242-6
Biochemical and biophysical research communications 2012 Sep 21;426(2):242-6
Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques.
Klatt NR, Canary LA, Vanderford TH, Vinton CL, Engram JC, Dunham RM, Cronise HE, Swerczek JM, Lafont BA, Picker LJ, Silvestri G, Brenchley JM
Journal of virology 2012 Jan;86(2):1203-13
Journal of virology 2012 Jan;86(2):1203-13
An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors.
Herschhorn A, Finzi A, Jones DM, Courter JR, Sugawara A, Smith AB 3rd, Sodroski JG
PloS one 2011;6(11):e26731
PloS one 2011;6(11):e26731
CD4-like immunological function by CD4- T cells in multiple natural hosts of simian immunodeficiency virus.
Vinton C, Klatt NR, Harris LD, Briant JA, Sanders-Beer BE, Herbert R, Woodward R, Silvestri G, Pandrea I, Apetrei C, Hirsch VM, Brenchley JM
Journal of virology 2011 Sep;85(17):8702-8
Journal of virology 2011 Sep;85(17):8702-8
C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif.
Andrew AJ, Kao S, Strebel K
The Journal of biological chemistry 2011 Nov 18;286(46):39967-81
The Journal of biological chemistry 2011 Nov 18;286(46):39967-81
Significant mobilization of both conventional and regulatory T cells with AMD3100.
Kean LS, Sen S, Onabajo O, Singh K, Robertson J, Stempora L, Bonifacino AC, Metzger ME, Promislow DE, Mattapallil JJ, Donahue RE
Blood 2011 Dec 15;118(25):6580-90
Blood 2011 Dec 15;118(25):6580-90
Direct antibody access to the HIV-1 membrane-proximal external region positively correlates with neutralization sensitivity.
Chakrabarti BK, Walker LM, Guenaga JF, Ghobbeh A, Poignard P, Burton DR, Wyatt RT
Journal of virology 2011 Aug;85(16):8217-26
Journal of virology 2011 Aug;85(16):8217-26
An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching.
Larsen CP, Page A, Linzie KH, Russell M, Deane T, Stempora L, Strobert E, Penedo MC, Ward T, Wiseman R, O'Connor D, Miller W, Sen S, Singh K, Kean LS
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2010 Nov;10(11):2396-409
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2010 Nov;10(11):2396-409
The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum.
Hsieh SC, Tsai WY, Wang WK
Journal of virology 2010 May;84(9):4782-97
Journal of virology 2010 May;84(9):4782-97
Novel role of plasmacytoid dendritic cells in humans: induction of interleukin-10-producing Treg cells by plasmacytoid dendritic cells in patients with rheumatoid arthritis responding to therapy.
Kavousanaki M, Makrigiannakis A, Boumpas D, Verginis P
Arthritis and rheumatism 2010 Jan;62(1):53-63
Arthritis and rheumatism 2010 Jan;62(1):53-63
DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas.
Lai AY, Fatemi M, Dhasarathy A, Malone C, Sobol SE, Geigerman C, Jaye DL, Mav D, Shah R, Li L, Wade PA
The Journal of experimental medicine 2010 Aug 30;207(9):1939-50
The Journal of experimental medicine 2010 Aug 30;207(9):1939-50
Multicolor flow cytometry analyses of cellular immune response in rhesus macaques.
He H, Courtney AN, Wieder E, Sastry KJ
Journal of visualized experiments : JoVE 2010 Apr 22;(38)
Journal of visualized experiments : JoVE 2010 Apr 22;(38)
Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor.
Kochenderfer JN, Feldman SA, Zhao Y, Xu H, Black MA, Morgan RA, Wilson WH, Rosenberg SA
Journal of immunotherapy (Hagerstown, Md. : 1997) 2009 Sep;32(7):689-702
Journal of immunotherapy (Hagerstown, Md. : 1997) 2009 Sep;32(7):689-702
Gammadelta T cell immune manipulation during chronic phase of simian-human immunodeficiency virus infection [corrected] confers immunological benefits.
Ali Z, Yan L, Plagman N, Reichenberg A, Hintz M, Jomaa H, Villinger F, Chen ZW
Journal of immunology (Baltimore, Md. : 1950) 2009 Oct 15;183(8):5407-17
Journal of immunology (Baltimore, Md. : 1950) 2009 Oct 15;183(8):5407-17
A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation.
Nguyen V, Cao L, Lin JT, Hung N, Ritz A, Yu K, Jianu R, Ulin SP, Raphael BJ, Laidlaw DH, Brossay L, Salomon AR
Molecular & cellular proteomics : MCP 2009 Nov;8(11):2418-31
Molecular & cellular proteomics : MCP 2009 Nov;8(11):2418-31
CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface.
Achour L, Scott MG, Shirvani H, Thuret A, Bismuth G, Labbé-Jullié C, Marullo S
Blood 2009 Feb 26;113(9):1938-47
Blood 2009 Feb 26;113(9):1938-47
Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease.
Freeman CM, Martinez FJ, Han MK, Ames TM, Chensue SW, Todt JC, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL
American journal of respiratory and critical care medicine 2009 Dec 15;180(12):1179-88
American journal of respiratory and critical care medicine 2009 Dec 15;180(12):1179-88
The Mi-2/NuRD complex associates with pericentromeric heterochromatin during S phase in rapidly proliferating lymphoid cells.
Helbling Chadwick L, Chadwick BP, Jaye DL, Wade PA
Chromosoma 2009 Aug;118(4):445-57
Chromosoma 2009 Aug;118(4):445-57
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.
Yamano Y, Araya N, Sato T, Utsunomiya A, Azakami K, Hasegawa D, Izumi T, Fujita H, Aratani S, Yagishita N, Fujii R, Nishioka K, Jacobson S, Nakajima T
PloS one 2009 Aug 5;4(8):e6517
PloS one 2009 Aug 5;4(8):e6517
The Ixodes scapularis salivary protein, salp15, prevents the association of HIV-1 gp120 and CD4.
Juncadella IJ, Garg R, Bates TC, Olivera ER, Anguita J
Biochemical and biophysical research communications 2008 Feb 29;367(1):41-6
Biochemical and biophysical research communications 2008 Feb 29;367(1):41-6
Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1.
Bour S, Boulerice F, Wainberg MA
Journal of virology 1991 Dec;65(12):6387-96
Journal of virology 1991 Dec;65(12):6387-96
Separation of functional subsets of human T cells by a monoclonal antibody.
Reinherz EL, Kung PC, Goldstein G, Schlossman SF
Proceedings of the National Academy of Sciences of the United States of America 1979 Aug;76(8):4061-5
Proceedings of the National Academy of Sciences of the United States of America 1979 Aug;76(8):4061-5
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- Fig. 3 Shed gp120 from productively infected cells is the major source of gp120 present on the surface of uninfected bystander CD4 + T cells. Detection of uninfected bystander primary CD4 + T cells infected with (a) NL4-3 GFP ADA wt virus or (b) CH77, by anti-gp120 Abs (A32, C11, 2G12; depicted in red) and anti-gp41 (F240) and anti-gp120-gp41 Abs (PGT151; depicted in blue) over the course of the infection. The data presented are representative of the results obtained in cells from at least two donors. (c,d) Uninfected cells, stained with the cellular dye eFluor 450, were co-cultured with unstained autologous mock-infected or HIV-1-infected cells. The ability of anti-Env Abs (A32, C11, 2G12, F240 and PGT151) to recognize uninfected bystander cells, designated as eFluor-450 + GFP - cells, was evaluated by FACS at 0, 24 and 48 h of co-culture. Shown in (c) are the gating strategy and a representative staining obtained with the A32 Ab. Shown in (d) are the quantification of the results obtained with at least 4 donors with all tested anti-Env Abs. Statistical significance was tested using the Mann-Whitney t test (*p < 0.05, **p < 0.01, ns: not significant).
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- Figure 7 Effects of TEX on protein expression and functions of T cells. In ( a ) down-regulation of CD69 protein expression on the surface of responder CD4 + Tconv after co-incubation with TEX. Activated CD4 + Tconv were co-incubated with TEX (10 ug protein) produced by the PCI-13 cells or with PBS for 12 h. The CD69 expression levels on CD4 + Tconv were then determined by flow cytometry (MFI) and were converted into MESF units based on calibration curves established with fluorescent calibration beads. The bar graphs show data (mean values +- SD) from 3 independent experiments performed with CD4 + Tconv obtained from different normal donors. The asterisks indicate p values at p < 0.0005. In ( b ) changes in expression levels of CD39 protein on the surface of resting CD4 + CD39 + Treg co-incubated with TEX produced by the PCI-13 cell line or DEX. The exosomes were used at the concentration of 10 ng protein/ assay. Exogenous ATP was added as described in Methods. Flow cytometry ( right ) shows up-regulation of MFI for CD39 in a representative experiment, and the bar graph summarizes results of three experiments performed with Treg obtained from different donors. In ( c ), Production levels of 5' AMP, adenosine and inosine by resting CD4 + CD39 + Treg co-incubated with TEX produced by the PCI-13 cell line. The data are from one of two experiments performed in the presence of exogenous ATP. The analyte levels were measured by mass spectrometry as described in Methods.
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- Figure 1. PS Expression on Immune Subsets in the Tumor Increases after RT C57BL/6 mice were injected with 100,000 B16F10 melanoma cells intradermally on the hindlimb. 10 days later, tumor-bearing hindlimbs received 15 Gy RT. 10 days thereafter, tumors were excised and analyzed by flow cytometry. (A) Schema and representative plots showing caspase-3/7 activity and PS expression on live (blue) versus dead (gray) tumor cells determined by a viability dye. (B) Representative gating strategy used to measure PS expression using viable CD8+ T cells from the tumor as an example. Gating was based on caspase-3/7 and annexin V fluorescence minus one (FMO). (C) Relative expression of PS on viable immune cell subsets in the tumors of mice with and without tumor-directed RT. (D) Frequencies of immune cells as a percentage of live CD45+ cells in the tumor with and without tumor-directed RT. The tables next to the figure legend lists the percentages shown in the pie charts. (E) Quantification of annexin V+ immune and tumor cells +-SEM (3-5 mice per group) from control tumors (white bars) and RT tumors (black bars). *p < 0.05.
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- Figure 2. EV quantification and cell origin in association with HIV. Purified plasma EVs fromuninfected (Control, n = 8) and HIV+ patients (n = 17) were stained with the lipophilic fluorescent tracer dye DiD to count total vesicles ( Figure 2A and B ), then labeled with antibodies directed against receptors CD45 ( Figure 2C and D ), CD4 ( Figure 2E and F ), and CD8 ( Figure 2 G and H ) to evaluate cell origin by cytofluorometry. Asterisks denote significant difference (** P
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- Figure 7 HEBCan Rescues Hematopoiesis and T Cell Development in HEB -/- hESCs in OP9-DL4 Co-cultures (A) qRT-PCR analysis for the expression of hematopoietic genes in CD34 + cells sorted from WT, KO + GFP, and KO + HEBCan day-8 (d8) EBs. mRNA levels are shown relative to GAPDH. (B and C) Percentages (B) and numbers (C) of CD45 + cells in d12 and d18 OP9-DL4 co-cultures. (D and E) Flow-cytometric analysis of T cell development from WT, KO + GFP, and KO + HEBCan d8 EB-derived CD34 + cells at d12 (D) and d18 (E) of OP9-DL4 co-culture. Cells are gated on the CD45 + DAPI - population. Error bars represent mean +- SD (n = 3 independent experiments). * p < 0.05, ** p < 0.01, *** p < 0.005 by Student's t test. Plots in (B), (D), and (E) are representative of three independent experiments.
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- Figure 1. Flow cytometric analysis was used to determine the distribution of Th22, Th17 and Th1 cells in EGC, HE and HY ( Fig. 1 ). Flow cytometric analysis of Th22, Th17 and Th1 cells in peripheral whole blood from EGC (n=39), HE (n=32) and HY (n=31). (A) Lymphocytes were gated in P1 using flow cytometry. CD4 + IFN-gamma - lymphocytes were gated in P2 using flow cytometry, and representative results of flow cytometric analyses for (B) Th1 (CD4 + IFN-gamma + ), (C) Th22 (CD4 + IFN-gamma - IL-17 - IL-22 + ) and Th17 (CD4 + IFN-gamma - IL-17 + IL-22 - ) cells in the three groups of subjects are presented. The number of cells stained in EGC, HE and HY in P2 were 2,654, 4,696 and 5,185, respectively. The proportion of (D) Th22, (E) Th17 and (F) Th1 cells in the three groups of subjects. The proportion of (G) Th22 and (H) Th17 cells in peripheral whole blood derived from patients with early (n=13) or advanced (n=26) gastric cancer. The association between the proportion of (I) Th22 and Th17 cells, (J) Th22 and Th1 cells, and (K) Th17 and Th1 cells, in peripheral whole blood of all subjects. *P
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- Fig. 1 CD46 co-stimulation provides superior support for CTL activity. a CD46 expression on the surface of resting human CD4 + and CD8 + T cells assessed by FACS analysis ( n = 4, gating strategy in Supplementary Fig. 7a ). b Comparison of IFN-gamma, TNF-alpha and IL-10 secretion by CD3 + CD46-activated T cells. Purified CD4 + and CD8 + T cells from healthy donors were left non-activated (NA) or stimulated with immobilized antibodies to CD3, CD3 + CD28 or CD3 + CD46 and cytokines measured 60 h post activation ( n = 5). c, d Degranulation (CD107a staining, ( c )) and granzyme B expression ( d ) by CD8 + T cells upon CD46 co-stimulation. CD8 + T cells were stimulated as in ( a ) and CD107a and granzyme B expression assessed with left panels showing representative cytometry images and right panels corresponding quantifications ( n = 3, gating strategy in Supplementary Fig. 7b ). e Killing activity of CD46-activated CD8 + T cells. T cells were stimulated as depicted for 24 h and cytotoxic activity of differently activated CD8 + T cells towards DU145 target cells assessed 24 h post co-culture of T cells and DU145 cells ( n = 4, gating strategy in Supplementary Fig. 7c ). f Effect of CD46 co-stimulation on CD8 + T-cell proliferation. Purified T cells were activated as indicated for 5 days and cell proliferation measured each day ( n = 4) (black circles, non-activated cells; green, blue, and red circles, CD3, CD3 + CD28 or CD3 + CD46-activated cells, res
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- Fig. 1 CD20 dim CD4 + T cells involve memory phenotypes with more activation than CD20 - cells. PBMC from uninfected donors, ART-suppressed patients and viremic patients were stained with CD20, activation markers (HLA-DR, CD69, CD25), and T-cell differentiation markers (CCR7, CD45RO, CD27, CD95). a Gating strategy used to identify CD20 dim CD4 + T cells. Previous sequential gates are represented in Supplementary Fig. 9 . Viable CD4 + T cells (identified by CD3 and CD4 expression) were first selected for the analysis of CD20 expression, defined by its Fluorescence Minus One (FMO) control. T-cell memory subsets were selected as follows: CD4 + T NA (CCR7 + , CD45RO - , CD27 + , CD95 - ), CD4 + T SCM (CCR7 + , CD45RO - , CD27 + , CD95 + ); CD4 + T CM (CCR7 + , CD45RO + ), CD4 + T TM (CCR7 - , CD45RO + , CD27 + ); CD4 + T EM (CCR7 - , CD45RO + , CD27 - ), CD4 + T TD (CCR7 - , CD45RO - ). b , c Representative bright-field and pseudo-color fluorescence images of CD20 dim CD4 + T cells ( b ) and B cells ( c ) from two ART-suppressed patients (#9 and #22) using the Amnis imaging flow cytometer technology. Scale bar 10 um. d Percentage of CD20 dim expression within CD4 + T cells in uninfected controls and the two patient cohorts. Mann-Whitney comparison was used to compare n = 6 uninfected controls, n = 21 ART-suppressed patients, n = 20 viremic patients. e Expression of the activation markers CD25, CD69 or HLA-DR in CD20 dim and CD20 - CD4 + T cells in different cohorts of HIV + patie
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- Fig. 5 Ex vivo infection upregulates CD20 expression. Unstimulated PBMCs from three uninfected donors were infected with HIV strain NL4.3. Infection was monitored by simultaneous staining of HIV RNA using the RNA FISH-flow assay and the viral protein p24 at days 3, 4, and 5. a Gating strategy used to monitor HIV infection and expression of CD20 dim . Previous sequential gates are represented in Supplementary Fig. 9 . b Percentage of productively HIV-infected cells in CD3 + T cells (left panel) and in CD20 dim or CD20 - CD3 + T cells (right panel). c Expression of CD20 dim in infected and uninfected CD3 + T cells (left panel) and in the total CD3 + T cell population (right panel). d Correlation between the proportion of infected cells within the CD3 + T cell population and CD20 expression (left panel) and the mean fluorescence intensity (MFI) of CD20 (right panel). e Percentage of HLA-DR and PD-1 in infected and uninfected cells expressing or not expressing CD20 dim . f Proportion of CD20 dim in infected cells expressing the CD4 cell receptor versus infected cells with marked downregulation of the CD4 receptor. In all panels, the mean and SEM value of three independent experiments is represented. In panel ( d ), Spearman's nonparametric correlation coefficients and associated p values are shown. Data underlying this Figure are provided as Source Data file
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- Figure 3 IHC analysis of paraffin-embedded tumor sections from patients with PDA or control pancreatic tissue. Magnification: 200x. Comparisons of FoxP3 + cell, CD8 + cell and CD4 + cell infiltrates between the juxtatumoral stroma and the panstroma. IHC analyzed the expression of Foxp3, CD4 and CD8 and statistical analysis the frequencies in juxtatumoral stroma and in panstroma. Comparisons between the two groups were assessed using Student's t test. NS, not significant; ** P
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- Figure 1 Anti-HER2 DARPin-Targeted CAR-T Cells Demonstrated Similarl Efficacy In Vitro (A) Schematics of the dual-promoter lentiviral (LV) gene cassettes used to generate anti-HER2 DARPin-targeted first- or second-generation CAR-T cells (structural details are as indicated; TM, transmembrane; IC, intracellular) or CAR-negative control NGFR-T cells. In all cases, truncated NGFR (tNGFR) is included as a transduction marker. (B) Expression of CARs on the surface of engineered (NGFR + ) T cells as determined by flow cytometry (upstream gating strategy: lymphocytes - singlets - NGFR + ). Mean fluorescence intensity (MFI) for CAR expression is indicated in brackets. Representative results have been replicated in 2-4 additional independent experiments. (C and D) Production of IFN-gamma (C) and TNF-alpha (D) upon CAR-T cell stimulation with HER2 + (OVCAR-3; closed symbols) or HER2 - (LOX-IMVI; open symbols) human tumor cell lines was measured by intracellular cytokine staining (ICS) and subsequent flow cytometry (upstream gating strategy: lymphocytes - singlets - CD4 + or CD8 + T cells). Percent cytokine production was normalized for transduction (transduction ranges observed: DARPin-28z, 39%-60%; DARPin-BBz, 33%-52%; DARPin-z, 25%-63%; NGFR, 63%-86%). Each point indicates data from a single independent experiment (n = 3-5 per LV construct); black lines indicate mean values. (E and F) Cytotoxicity across various effector:target (E:T) ratios with LOX-IMVI (E) or OVCAR-3 (F) tumor cell
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- Figure 3 DAPRin-28z-T Cells Activated in the Lungs and Heart, Resulting in a Systemic Cytokine Storm OVCAR-3 tumor-bearing NRG mice were treated with 6 x 10 6 effective DARPin-28z-T cells or a matched number of NGFR-T cells. (A-C) Mice were sacrificed at 1, 3, or 5 days post-ACT1 for total body perfusion, fixation, necropsy, and histological analysis. (A) Hematoxylin and eosin (H&E) staining of the lungs at 20x magnification (scale bars, 100 mum). V, vasculature. (B) Immunohistochemistry (IHC) for human CD3 in the lungs at 20x magnification (scale bars, 100 mum) or 60x magnification (zoom-in; scale bars, 50 mum). (C) H&E or CD3 IHC staining of the heart at 20x magnification (scale bars, 100 mum); arrow indicates aberrant region of inflammation along the right heart wall. Representative images from n = 2-3 mice are shown. Findings have been recapitulated in 1-2 additional independent experiments. (D) DARPin-28z- or NGFR-T cells were co-cultured with tumor-free NRG mouse lung homogenates ex vivo . T cell proliferation was measured by flow cytometry using CellTrace Violet (CTV) dye. Data are representative of two independent experiments. (E) Mice were bled at 1, 3, 5, or 7 days post-ACT1 for multiplex analysis of human serum cytokine content; a globally normalized heatmap of log2-transformed human cytokine fluorescence readings is shown. Each square represents data from one mouse. Colorimetric scale bar indicates minimum, average, and maximum values on map. Absolute values are d
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- Figure 4 Differential In Vivo Toxicity of DARPin-28z-T Cells Manufactured from Unique PBMC Donors Correlated with the Frequency of CD4+ T Cells in the Adoptive Transfer Product (A) OVCAR-3 tumor-bearing NRG mice were treated with 6.0 x 10 6 or 1.7-2.0 x 10 6 DARPin-28z-T cells produced from MAC026, LEUK001, or MAC014 PBMCs. Mice were monitored over time for changes in weight. Data were pooled from n = x independent experiments. For 6.0 x 10 6 cells, MAC014, 2; LEUK001, 3; and MAC026, 4. For 2.0 x 10 6 cells, MAC014, 1; LEUK001, 2; and MAC026, 1. Each line indicates data from one animal; curves end, indicating when mice succumbed to toxicity. (B) Composition of CD4 + or CD8 + cells in DARPin-28z-T cell products (days 13-14 post-activation) manufactured using starting PBMCs from donors as indicated and determined using flow cytometry (upstream gating strategy: lymphocytes - singlets - NGFR + ). Error bars represent SD. Data from n = x independent experiments; MAC014, 5 (2 unique PBMC preparations); LEUK001, 6 (1 PBMC preparation); and MAC026, 12 (5 unique PBMC preparations).
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- Figure 6 Enhanced proliferation and IFNgamma release of CD4+ T cells induced by moDCs stimulated with supernatant of NB-PDT treated tumor cells. A431 cells were treated with NB-PDT, the supernatant was collected 24 h later and incubated with immature moDCs for another 24 h. moDCs were then co- incubated with allogeneic CFSE-labeled CD4+ T cells in a 1:10 ratio. After 6 days, CD4+ T cell proliferation was measured with flow cytometry and IFNgamma release was assessed by ELISA. ( a ), Percentage of CD4+ T cells with weak CFSE signal, thus proliferating cells (n = 4). ( b ), Quantification of released IFNgamma by CD4+ T cells (n = 3). Each combination of allogeneic donors is represented by a different symbol and color. ctr, unstimulated DCs; LPS, LPS-stimulated DCs; NT, untreated tumor cells; LD50, mild cytotoxic NB-PDT; LD100, highly cytotoxic NB-PDT; Light, only light control; NB-PS, only NB-PS conjugate control. Significance is displayed as * p