Costimulation Light: Activation of CD4+ T Cells with CD80 or CD86 Rather Than Anti-CD28 Leads to a Th2 Cytokine Profile
To examine the role of CD28 and CTLA-4 in Th cell differentiation, we used a novel microsphere-based system to compare the effects of CD28 ligation by Ab or CD80/CD86. One set of beads was prepared by coating with anti-CD3 and anti-CD28 Ab. Another set of beads was prepared by immobilizing anti-CD3...
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creator | Broeren, Chris P. M Gray, Gary S Carreno, Beatriz M June, Carl H |
description | To examine the role of CD28 and CTLA-4 in Th cell differentiation, we used a novel microsphere-based system to compare the effects of CD28 ligation by Ab or CD80/CD86. One set of beads was prepared by coating with anti-CD3 and anti-CD28 Ab. Another set of beads was prepared by immobilizing anti-CD3 and murine CD80-Ig fusion protein or murine CD86-Ig fusion protein on the beads. The three sets of beads were compared in their effects on the ability to activate and differentiate splenic CD4 T cells. When purified naive CD4(+) cells were stimulated in vitro, robust proliferation of similar magnitude was induced by all three sets of beads. When cytokine secretion was examined, all bead preparations induced an equivalent accumulation of IL-2. In contrast, there was a marked difference in the cytokine secretion pattern of the Th2 cytokines IL-4, IL-10, and IL-13. The B7-Ig-stimulated cultures had high concentrations of Th2 cytokines, whereas there were low or undetectable concentrations in the anti-CD28-stimulated cultures. Addition of anti-CTLA-4 Fab augmented B7-mediated IL-4 secretion. These studies demonstrate that B7 is a critical and potent stimulator of Th2 differentiation, and that anti-CD28 prevents this effect. |
doi_str_mv | 10.4049/jimmunol.165.12.6908 |
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In contrast, there was a marked difference in the cytokine secretion pattern of the Th2 cytokines IL-4, IL-10, and IL-13. The B7-Ig-stimulated cultures had high concentrations of Th2 cytokines, whereas there were low or undetectable concentrations in the anti-CD28-stimulated cultures. Addition of anti-CTLA-4 Fab augmented B7-mediated IL-4 secretion. 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M</creatorcontrib><creatorcontrib>Gray, Gary S</creatorcontrib><creatorcontrib>Carreno, Beatriz M</creatorcontrib><creatorcontrib>June, Carl H</creatorcontrib><title>Costimulation Light: Activation of CD4+ T Cells with CD80 or CD86 Rather Than Anti-CD28 Leads to a Th2 Cytokine Profile</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>To examine the role of CD28 and CTLA-4 in Th cell differentiation, we used a novel microsphere-based system to compare the effects of CD28 ligation by Ab or CD80/CD86. One set of beads was prepared by coating with anti-CD3 and anti-CD28 Ab. Another set of beads was prepared by immobilizing anti-CD3 and murine CD80-Ig fusion protein or murine CD86-Ig fusion protein on the beads. The three sets of beads were compared in their effects on the ability to activate and differentiate splenic CD4 T cells. When purified naive CD4(+) cells were stimulated in vitro, robust proliferation of similar magnitude was induced by all three sets of beads. When cytokine secretion was examined, all bead preparations induced an equivalent accumulation of IL-2. In contrast, there was a marked difference in the cytokine secretion pattern of the Th2 cytokines IL-4, IL-10, and IL-13. The B7-Ig-stimulated cultures had high concentrations of Th2 cytokines, whereas there were low or undetectable concentrations in the anti-CD28-stimulated cultures. Addition of anti-CTLA-4 Fab augmented B7-mediated IL-4 secretion. These studies demonstrate that B7 is a critical and potent stimulator of Th2 differentiation, and that anti-CD28 prevents this effect.</description><subject>Abatacept</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - physiology</subject><subject>Antigens, Differentiation - metabolism</subject><subject>B7-1 Antigen - immunology</subject><subject>B7-1 Antigen - physiology</subject><subject>B7-2 Antigen</subject><subject>Binding Sites, Antibody</subject><subject>CD28 Antigens - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cells, Cultured</subject><subject>CTLA-4 Antigen</subject><subject>Cytokines - biosynthesis</subject><subject>Female</subject><subject>Immune Sera - metabolism</subject><subject>Immune Sera - pharmacology</subject><subject>Immunoconjugates</subject><subject>Immunologic Memory</subject><subject>Interleukin-4 - biosynthesis</subject><subject>Interphase - immunology</subject><subject>Lymphocyte Activation - immunology</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microspheres</subject><subject>Muromonab-CD3 - pharmacology</subject><subject>Solubility</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkFGL1DAQx4Mo3nr6DUTyJAfSdSZNk5xvS089YUGR9TmkbWpzts2ZpJb79mbZFe9pYOY3_2F-hLxG2HLg1-_v3DQtsx-3KKotsq24BvWEbLCqoBACxFOyAWCsQCnkBXkR4x0ACGD8OblARAYKxYastY_JTctokvMz3bufQ_pAd21yf04d39P6hr-jB1rbcYx0dWnIHQXUh2MV9LtJgw30MJiZ7ubkivqGKbq3pos0eWryhNH6Iflfbrb0W_C9G-1L8qw3Y7SvzvWS_Pj08VDfFvuvn7_Uu33RloqlQimw2JmubNXxaVDSSMHbpukRmw6kFKisgRK6UnVctmWfcSkqVjWooC_LS_L2lHsf_O_FxqQnF9v8iZmtX6KWjCueozPIT2AbfIzB9vo-uMmEB42gj7f1P-E6C9fI9FF4Xntzzl-ayXb_l86GM3B1AoasdnXB6jiZccw46nVdH2f9BaE8iNk</recordid><startdate>20001215</startdate><enddate>20001215</enddate><creator>Broeren, Chris P. 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M</au><au>Gray, Gary S</au><au>Carreno, Beatriz M</au><au>June, Carl H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Costimulation Light: Activation of CD4+ T Cells with CD80 or CD86 Rather Than Anti-CD28 Leads to a Th2 Cytokine Profile</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2000-12-15</date><risdate>2000</risdate><volume>165</volume><issue>12</issue><spage>6908</spage><epage>6914</epage><pages>6908-6914</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>To examine the role of CD28 and CTLA-4 in Th cell differentiation, we used a novel microsphere-based system to compare the effects of CD28 ligation by Ab or CD80/CD86. One set of beads was prepared by coating with anti-CD3 and anti-CD28 Ab. Another set of beads was prepared by immobilizing anti-CD3 and murine CD80-Ig fusion protein or murine CD86-Ig fusion protein on the beads. The three sets of beads were compared in their effects on the ability to activate and differentiate splenic CD4 T cells. When purified naive CD4(+) cells were stimulated in vitro, robust proliferation of similar magnitude was induced by all three sets of beads. When cytokine secretion was examined, all bead preparations induced an equivalent accumulation of IL-2. In contrast, there was a marked difference in the cytokine secretion pattern of the Th2 cytokines IL-4, IL-10, and IL-13. The B7-Ig-stimulated cultures had high concentrations of Th2 cytokines, whereas there were low or undetectable concentrations in the anti-CD28-stimulated cultures. Addition of anti-CTLA-4 Fab augmented B7-mediated IL-4 secretion. 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subjects | Abatacept Animals Antibodies, Monoclonal - metabolism Antigens, CD - immunology Antigens, CD - physiology Antigens, Differentiation - metabolism B7-1 Antigen - immunology B7-1 Antigen - physiology B7-2 Antigen Binding Sites, Antibody CD28 Antigens - immunology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cells, Cultured CTLA-4 Antigen Cytokines - biosynthesis Female Immune Sera - metabolism Immune Sera - pharmacology Immunoconjugates Immunologic Memory Interleukin-4 - biosynthesis Interphase - immunology Lymphocyte Activation - immunology Membrane Glycoproteins - immunology Membrane Glycoproteins - physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Microspheres Muromonab-CD3 - pharmacology Solubility T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism |
title | Costimulation Light: Activation of CD4+ T Cells with CD80 or CD86 Rather Than Anti-CD28 Leads to a Th2 Cytokine Profile |
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