Interleukin 15 Controls both Proliferation and Survival of a Subset of Memory-Phenotype CD8⁺ T Cells

Previous work has shown that memory-phenotype CD44^hi CD8⁺ cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44^hi CD8⁺ cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44^hi CD8⁺ cells comprise a mixed population of IL-15–dependent and IL-15–independent cells. The major subset of CD122^hi CD44^hi CD8⁺ cells is heavily dependent on IL-15 by three different parameters, namely (1) “bystander” proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal “background” proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49⁺ subset of CD122^hi CD44^hi CD8⁺ cells. In contrast to CD122^hi cells, the CD122^lo subset of CD44^hi CD8⁺ cells is IL-15 independent; likewise, being CD122^lo, CD44^hi CD4⁺ cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.