Additional loss of Bim rescues viral-specific effector and memory T cells, but not endogenous memory T cells or NK cells in IL-15-deficient mice (150.10)

Abstract

Abstract IL-15 is γc cytokine well appreciated for its role in the homeostasis of memory CD8+ T cells and survival of NK cells. IL-15 drives homeostatic proliferation of memory phenotype (CD44hi CD122hi) and antigen specific memory CD8+ T cells. We and others have recently shown that IL-15 regulates survival of a subset of effector CD8+ T cells (KLRG1hi CD127lo) and acts redundantly with IL-7 for the survival of KLRG1lo CD127hi effector CD8+ T cells. Mechanistically, IL-15 is thought to maintain T cells by elevating Bcl-2 expression. Further, enforced expression of Bcl-2 can prevent the loss of effector CD8+ T cells in IL-15-deficient mice. Here, we examined whether deficiency of the pro-apoptotic BH3-only molecule Bim could prevent the loss of NK cells and memory CD8+ T cells in IL-15-deficient mice. We found that lack of Bim did not prevent the loss of NK cells and endogenous memory (CD44hi CD122hi) CD8+ T cells in the absence of infection. However, when we analyzed antigen-specific responses following infection with lymphocytic choriomeningitis virus (LCMV), we found that deletion of Bim partially rescued the survival of KLRG1hi CD127lo effector CD8+ T cells in the absence of IL-15. In addition, deletion of Bim completely rescued the loss of functional LCMV-specific memory CD8+ T cells. Our results indicate that IL-15 exerts its homeostatic effects through different mechanisms for the maintenance of endogenous memory phenotype and antigen-specific CD8+ T cells.