PARTIAL SIGNALING BY CYTOKINES - CYTOKINE REGULATION OF CELL-CYCLE AND FAS-DEPENDENT, ACTIVATION-INDUCED DEATH IN CD4(+) SUBSETS

Fas-dependent, activation-induced death (AID) of T cells has been impl icated in the regulation of peripheral T cell populations. We have pre viously reported that IL-2 plays a unique role in regulating sensitivi ty to AID in primary CD4(+) cells. In this report we have compared the capacity of IL-2, IL-4, and IL-7 to increase entry into cell cycle vs their capacity to increase sensitivity to AID. Our data indicate that IL-2 plays a unique role ill the regulation of ATD in both Th1 and Th 2 subsets and that with a given AID stimulus, cell cycle progression i s necessary, but not sufficient, for ALD, Interestingly, induction of cell cycle entry and sensitivity to ALD can be dissociated (partial si gnaling) not only with different cytokines, but, even with point mutat ions in IL-2 itself. This provides the first evidence that cytokine va riants or pharmacological agents that mimic their action will he usefu l in enhancing selective elements of pleiotropic cytokine actions. (C) 1997 Academic Press.