IL-7 enhances the survival and maintains the size of naive T cells.
T cells require continual presence of extrinsic signals from their in vivo microenvironment to maintain viability. T cells removed from these signals and placed in tissue culture atrophied and died in a caspase-independent manner. Atrophy was characterized by smaller cell sizes, delayed mitogenic responses, and decreased glycolytic rate. Bcl-2 expression remained constant in vitro despite ongoing cell death, indicating that endogenous Bcl-2 expression is insufficient to explain the life span and size control of lymphocytes in vivo and that cell-extrinsic signals provided may be required to maintain both cell viability and size in vivo. One such signal, IL-7, was found to maintain both the size and survival of neglected T cells in vitro. IL-7 was not unique, because the common gamma-chain cytokines IL-2, IL-4, and IL-15, as well as the gp130 cytokine IL-6, also promoted both T cell survival and size maintenance. IL-7 did not induce resting T cells to proliferate. Instead, IL-7 stimulated neglected T cells to maintain their metabolic rate at levels comparable to freshly isolated cells. The survival and trophic effects of IL-7 could be separated because IL-7 was able to promote up-regulation of Bcl-2 and maintain cell viability independent of phosphatidylinositol 3-kinase and mammalian target of rapamycin activity but was unable to prevent cellular atrophy when phosphatidylinositol 3-kinase and mammalian target of rapamycin were inhibited. These data demonstrate that T cells require the continuous presence of extrinsic signals not only to survive but also to maintain their size, metabolic activity, and the ability to respond rapidly to mitogenic signals.
Rathmell
J C
JC
Department of Cancer Biology and Medicine and Abramson Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Farkash
E A
EA
Gao
W
W
Thompson
C B
CB
D000818:Animals; D020169:Caspases / Q000502:physiology; D016923:Cell Death; D002455:Cell Division; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D020169:Caspases; D016207:Cytokines; D005947:Glucose; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D058570:TOR Serine-Threonine Kinases; C507942:Il2rg protein, mouse; C546843:mTOR protein, mouse