In vitro induction of T cell anergy by blocking B7 and early T cell costimulatory molecule ETC-1/B7-2.
APC-associated B7 and ETC-1/B7-2 are two major costimulatory molecules for full activation of T lymphocytes during auto- and allogeneic immune responses. In this report, we further examine the role of the two molecules in murine CD4+ T cell activation and anergy development. As suggested in antibody blocking studies, optimal activation of CD4+ T cells in response to anti-CD3 stimulation requires collaborative signaling through the two molecules. Simultaneous blockade of B7 and ETC-1/B7-2 renders CD4+ T cells unresponsive to anti-CD3 restimulation. PCR analysis and cytokine reconstitution studies show that the observed unresponsiveness is correlated to a significant reduction of Th1-type cytokine production, suggesting B7 and ETC-1/B7-2-mediated costimulatory signaling may be specifically active in regulation of the function of the Th1 subset.
Chen
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Department of Inflammation and Autoimmune Diseases, Hoffmann-La Roche Research Center, Nutley, New Jersey 07110.
Nabavi
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D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D015398:Signal Transduction
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma