CD4(-CELLS REACTIVATED WITH SUPERANTIGEN ARE BOTH MORE SENSITIVE TO FASL-MEDIATED KILLING AND EXPRESS A HIGHER-LEVEL OF FASL() T)

Naive CD4(+) T cells proliferate strongly in response to superantigens such as staphylococcal enterotoxin B (SEE). When these cells are rest ed and challenged a second time, they undergo activation-induced cell death (AICD). Fas/FasL interactions have been shown to mediate AICD, e ven though the level of Fas expression in the 2 degrees SEE responder populations is no higher than in the 1 degrees cultures, To determine whether the dissimilarity between the 1 degrees and 2 degrees cultures could be attributed to differences in Fast cytotoxic activity or in t he sensitivity of the Fas apoptosis signaling pathway, we compared the se parameters during the 1 degrees and 2 degrees responses of lpr and gld CD4(+) T cells (which do not undergo AICD due to a lack of Fas and an inactive Fast, respectively) so that each parameter could be evalu ated independently, The results demonstrate that 2 degrees responders both express a higher level of functional Fast and are more sensitive to Fast-mediated killing. These findings account for the differences b etween the 1 degrees and 2 degrees responses of CD4(+) T cells to supe rantigen. In addition, we found that the apparent level of Fast-mediat ed cytotoxic activity in the 2 degrees lpr CD4(+) T cell population is much higher than that of wild-type cells, suggesting that deficient F as expression leads to inordinately high levels of Fast expression or subsaturation of Fast binding sites. (C) 1997 Academic Press.