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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Veröffentlicht in:The Journal of immunology (1950) 2000-12, Vol.165 (12), p.6908-6914
Hauptverfasser: Broeren, Chris P. M, Gray, Gary S, Carreno, Beatriz M, June, Carl H
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container_issue 12
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container_title The Journal of immunology (1950)
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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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ispartof The Journal of immunology (1950), 2000-12, Vol.165 (12), p.6908-6914
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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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