Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival.
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 IL7Ralpha 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 IL7Ralpha 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.
Experimental Immunology Branch, National Cancer Institute, Building 10 Room 4B36, Bethesda, Maryland 20892, USA.
Jung-Hyun
JH
Park
Qing
Q
Yu
Batu
B
Erman
Jacob S
JS
Appelbaum
Diego
D
Montoya-Durango
H Leighton
HL
Grimes
Alfred
A
Singer
D000818:Animals; D002470:Cell Survival / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D015851:Interleukin-7; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain