Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4.
Although much is known about the activation, proliferation, and function of CD4(+) T cells, little is known about how they survive as resting T cells in animals. Resting T cells have a half-life in animals of more than a week; however, when they are removed from animals and placed in tissue culture their half-life falls to approximately 24 h. In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7). They may do this in part by maintaining levels of survival-promoting proteins such as Bcl-2 in the cells, because the levels of Bcl-2 and Bcl-Xl in resting T cells fall rapidly after the cells are isolated from animals, and are maintained by culture in IL-4. Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival. Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner. These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.
Vella
A
A
Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Teague
T K
TK
Ihle
J
J
Kappler
J
J
Marrack
P
P
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D050800:STAT6 Transcription Factor; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*
D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4