CD4+ T cells reactivated with superantigen are both more sensitive to FasL-mediated killing and express a higher level of FasL

Abstract

Naive CD4+ T cells proliferate strongly in response to superantigens such as staphylococcal enterotoxin B (SEB). When these cells are rested and challenged a second time, they undergo activation-induced cell death (AICD). Fas/FasL interactions have been shown to mediate AICD, even though the level of Fas expression in the 2°SEB responder populations is no higher than in the 1°cultures. To determine whether the dissimilarity between the 1°and 2°cultures could be attributed to differences in FasL cytotoxic activity or in the sensitivity of the Fas apoptosis signaling pathway, we compared these parameters during the 1°and 2°responses of lpr and gld CD4+ T cells (which do not undergo AICD due to a lack of Fas and an inactive FasL, respectively) so that each parameter could be evaluated independently. The results demonstrate that 2°responders both express a higher level of functional FasL and are more sensitive to FasL-mediated killing. These findings account for the differences between the 1°and 2°responses of CD4+ T cells to superantigen. In addition, we found that the apparent level of FasL-mediated cytotoxic activity in the 2°lpr CD4+ T cell population is much higher than that of wild-type cells, suggesting that deficient Fas expression leads to inordinately high levels of FasL expression or subsaturation of FasL binding sites.