TY - JOUR
T1 - Partial signaling by cytokines
T2 - Cytokine regulation of cell cycle and fas-dependent, activation-induced death in CD4+ subsets
AU - Wang, Ruduan
AU - Ciardelli, Thomas L.
AU - Russell, John H.
N1 - Funding Information:
The authors thank Drs. Judy Giri and Steve Dowdy for critical review of the manuscript. This work was supported by USPHS Grants CA28533 (J.H.R.) and GM52858 and AI34331 (T.L.C.) and by Veterans Administration Grant VA002403234 (T.L.C.).
PY - 1997/12/15
Y1 - 1997/12/15
N2 - Fas-dependent, activation-induced death (AID) of T cells has been implicated in the regulation of peripheral T cell populations. We have previously reported that IL-2 plays a unique role in regulating sensitivity 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 in the regulation of AID in both Th1 and Th2 subsets and that with a given AID stimulus, cell cycle progression is necessary, but not sufficient, for AID. Interestingly, induction of cell cycle entry and sensitivity to AID can be dissociated (partial signaling) not only with different cytokines, but even with point mutations in IL-2 itself. This provides the first evidence that cytokine variants or pharmacological agents that mimic their action will be useful in enhancing selective elements of pleiotropic cytokine actions.
AB - Fas-dependent, activation-induced death (AID) of T cells has been implicated in the regulation of peripheral T cell populations. We have previously reported that IL-2 plays a unique role in regulating sensitivity 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 in the regulation of AID in both Th1 and Th2 subsets and that with a given AID stimulus, cell cycle progression is necessary, but not sufficient, for AID. Interestingly, induction of cell cycle entry and sensitivity to AID can be dissociated (partial signaling) not only with different cytokines, but even with point mutations in IL-2 itself. This provides the first evidence that cytokine variants or pharmacological agents that mimic their action will be useful in enhancing selective elements of pleiotropic cytokine actions.
UR - https://www.scopus.com/pages/publications/17944397260
U2 - 10.1006/cimm.1997.1220
DO - 10.1006/cimm.1997.1220
M3 - Article
C2 - 9514696
AN - SCOPUS:17944397260
SN - 0008-8749
VL - 182
SP - 152
EP - 160
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -