Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking
alloantigen-induced T-cell activation
SW Van Gool, JL Ceuppens, H Walter and M de Boer
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Costimulatory signals are absolutely required for T-cell activation after
T-cell receptor/major histocompatibility complex-peptide interaction. So
far, the best-known candidate essential costimulatory signal is mediated by
interaction of CD28 on T cells with B7 on antigen- presenting cells. Using
an allogeneic B7+ Epstein-Barr virus- transformed B-cell line as
stimulator, we found that addition of a monoclonal antibody (MoAb) to B7
that efficiently blocks B7-CD28 interaction only partially inhibited
proliferation and interleukin-2 (IL-2) production in primary and secondary
mixed lymphocyte reactions (MLR), whereas the generation of cytotoxic T
lymphocytes (CTL) was not affected. Inhibition of primary or secondary
MLR-induced T-cell activation with cyclosporin A (CsA) at nontoxic
concentrations also was never complete. However, the combination of CsA and
anti-B7 MoAb B7-24 synergistically blocked allogeneic B cell-induced T-cell
proliferation, IL-2 production, and CTL generation. These data suggest that
the mere blockage of B7-CD28 interaction during allotransplantation will be
insufficient to prevent rejection or graft-versus-host disease. However,
low CsA concentrations, when combined with an agent blocking B7-CD28
interaction, can potentially achieve complete immunosuppression.
Volume 83,
Issue 1,
pp. 176-183,
01/01/1994
Copyright © 1994 by The American Society of Hematology
