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 is 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.