The lymphopenic environment of CD132 (common gamma-chain)-deficient hosts elicits rapid homeostatic proliferation of naive T cells via IL-15.
Homeostatic proliferation for naive T cells is observed readily only under lymphopenic conditions in response to elevated levels of IL-7 and contact with self-MHC/peptide ligands. Homeostatic proliferation occurs at a slow pace and gradually induces the dividing cells to acquire characteristics of memory cells. We describe a novel type of homeostatic proliferation whereby naive T cells proliferate at a significantly faster rate, resembling the proliferation speed induced by foreign Ags, and the expanding cells rapidly differentiate into central memory cells. Remarkably, such rapid homeostatic proliferation is driven by a combination of IL-2 and IL-15, with IL-15 playing a bigger role, and applies for a wide repertoire of CD8(+) naive T cells, including many TCR-transgenic lines, even those that fail to undergo IL-7-driven homeostatic proliferation. Thus, naive T cells can be induced to undergo homeostatic proliferation of variable speed with a few members of the common gamma-chain (CD132) family of cytokines, the speed of proliferation depending on the levels of the particular cytokine involved.
Ramsey
Chris
C
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rubinstein
Mark P
MP
Kim
David M
DM
Cho
Jae-Ho
JH
Sprent
Jonathan
J
Surh
Charles D
CD
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D006706:Homeostasis; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology / Q000378:metabolism*; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic
D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7