Fas (CD95)/Fas ligand interactions regulate antigen-specific, major histocompatibility complex-restricted T/E cell proliferative responses

The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed. activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein. an inhibitor of FasL-mediated cytotoxicity. to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to Fast cytotoxicity. Moreover. both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that Fast cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.