The combination of anti-B7 monoclonal antibody and cyclosporin A induces alloantigen-specific anergy during a primary mixed lymphocyte reaction.
Interaction of CD28/CTLA-4 on T cells with B7 on antigen-presenting cells constitutes an important costimulatory signal for T cells and is responsible for cyclosporin A-resistant interleukin 2 (IL-2) gene expression and potentially also for prevention of anergy induction after T cell receptor triggering. In this paper, we demonstrate that addition of a monoclonal antibody to B7, which blocks B7-CD28/CTLA-4 interaction, and of cyclosporin A together, but not separately, to a primary mixed lymphocyte reaction of freshly isolated human T cells towards a human B cell line, induces nonresponsiveness of alloantigen-specific cytotoxic T lymphocyte precursors, whereas reactivity to a third party stimulator is intact. Nonresponsiveness could be reversed by culture in IL-2, indicating that anergy, and not clonal deletion, is responsible for this phenomenon. Our finding opens important perspectives for the development of new therapeutic strategies in transplantation.
Van Gool
S W
SW
Department of Internal Medicine, Catholic University of Leuven, Belgium.
de Boer
M
M
Ceuppens
J L
JL
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D002461:Cell Line, Transformed; D017635:Clonal Anergy / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine