[PDF][PDF] Suppression of IL7Rα transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival

JH Park, Q Yu, B Erman, JS Appelbaum… - Immunity, 2004 - cell.com
Immunity, 2004cell.com
Survival of naive T cells is dependent upon IL-7, which is present in vivo in limiting amounts
with the result that naive T cells must compete for IL-7-mediated survival signals. It would
seem imperative during T cell homeostasis that limiting IL-7 be shared by the greatest
possible number of T cells. We now describe a novel regulatory mechanism that specifically
suppresses IL7Rα transcription in response to IL-7 and other prosurvival cytokines (IL-2, IL-
4, IL-6, and IL-15). Consequently, IL7R expression is reduced on T cells that have received …
Abstract
Survival of naive T cells is dependent upon IL-7, which is present in vivo in limiting amounts with the result that naive T cells must compete for IL-7-mediated survival signals. It would seem imperative during T cell homeostasis that limiting IL-7 be shared by the greatest possible number of T cells. We now describe a novel regulatory mechanism that specifically suppresses IL7Rα transcription in response to IL-7 and other prosurvival cytokines (IL-2, IL-4, IL-6, and IL-15). Consequently, IL7R expression is reduced on T cells that have received cytokine-mediated survival signals so they do not compete with unsignaled T cells for remaining IL-7. Interestingly, cytokine-mediated suppression of IL7Rα transcription involves different molecular mechanisms in CD4+ and CD8+ T cells, as CD8+ T cells utilize the transcriptional repressor GFI1 while CD4+ T cells do not. We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available.
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