Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.
The overall size and composition of the pool of naive and memory T cells are tightly regulated by homeostatic mechanisms. Recent work has shown that homeostasis of naive T cells is controlled by two factors, self-major histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)-7. In particular, contact with these two factors is required for naive CD4+ and CD8+ cells to undergo "homeostatic" proliferation, i.e., proliferation induced as a consequence of severe T cell depletion. In contrast to naive T cells, the factors that drive memory T cells to undergo homeostatic proliferation are poorly understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells from normal mice were adoptively transferred into various gene-knockout mice rendered T cell-deficient by sublethal irradiation. Three findings are reported. First, unlike naive T cells, homeostatic proliferation of memory T cells is largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL-15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells, homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15 (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct.
Tan
Joyce T
JT
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ernst
Bettina
B
Kieper
William C
WC
LeRoy
Eric
E
Sprent
Jonathan
J
Surh
Charles D
CD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007156:Immunologic Memory / Q000502:physiology*; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D019409:Interleukin-15; D015851:Interleukin-7