THE ROLES OF COSTIMULATION AND FAS IN T-CELL APOPTOSIS AND PERIPHERALTOLERANCE

Using cells from TCR transgenic mice that do or do not express Fas, we show that there are two mechanistically distinct forms of apoptosis i n CD4(+) T cells. Naive T cells undergo apoptosis if cultured in the a bsence of antigen or costimulation. This form of programmed cell death (PCD) is not dependent on Fas, and is prevented by CD28-mediated sign als, which lead to the secretion of growth factors and the expression of survival genes, such as bcl-x(L). Recently activated T cells underg o apoptotic death upon repeated stimulation. This activation-induced c ell death (AICD) is mediated by Fas, but is independent of costimulati on and is not prevented by IL-2 or bcl-x(L). Finally, we show that per ipheral tolerance may be induced in vivo independent of Fas-mediated c ell death.