ACTIVATION OF HUMAN T-CELLS WITH SUPERANTIGEN (STAPHYLOCOCCAL-ENTEROTOXIN-B) AND CD28 CONFERS RESISTANCE TO APOPTOSIS VIA CD95

Ag recognition is an essential component for an effective T cell respo nse. However, T cell activation is also subject to additional regulati on by accessory molecules, CD28 prov-ides essential costimulatory sign als that allow T cells to proliferate, whereas molecules such as CTLA- 4 and CD95 (Fas) appear to be negative regulators, Currently, which ou tcome predominates under conditions of antigenic challenge is poorly u nderstood, In particular it has been suggested that one consequence of antigenic activation of T cells is the up-regulation of both CD95 and CD95 ligand, thereby exposing activated T cells to apoptotic death. W e have investigated this possibility in normal human peripheral blood T cells triggered by the superantigen SEE either in the presence of en dogenous APCs or transfectants expressing DR4 and CD80. In either case , we find that such activation does not expose the majority of T cells to anti-CD95-induced apoptosis as detected by annexin V externalizati on and DNA fragmentation, Furthermore, by phenotypically identifying, by how cytometry, those cells that received both antigenic and costimu latory signals from those cells that did not, we observed that CD95-in duced apoptosis was not seen in activated T cells receiving Ag and cos timulatory signals via CD28, However, while not all T cells were stimu lated by superantigen, CD95 expression was found to be homogeneously u p-regulated, suggesting a mechanism whereby bystander cells might be m ade susceptible to CD95-induced death, We conclude that antigenic acti vation of T cells via the TCR and CD28 engagement provides protection from CD95-induced apoptosis.