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.
Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking alloantigen-induced T-cell activation
- Share Icon Share
- Tools Icon Tools
- Search Site
- PDF LinkPDF
SW Van Gool, JL Ceuppens, H Walter, M de Boer; Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking alloantigen-induced T-cell activation. Blood 1994; 83 (1): 176–183. doi: https://doi.org/10.1182/blood.V83.1.176.bloodjournal831176
Download citation file: