Homeostatic proliferation but not the generation of virus specific memory CD8 T cells is impaired in the absence of IL-15 or IL-15Ralpha.

The generation and efficient maintenance of antigen specific memory T cells is essential for long-lasting immunological protection. Antigen specific memory CD8 T cells are known to be maintained via antigen-independent homeostatic proliferation. However, signals that drive memory T cell generation and/or influence the slow turnover of memory T cells are unknown. Recently, IL-15 has received attention for its potential effect on memory CD8 T cells. In this report we examine the role of IL-15 in the generation and maintenance of virus specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor a chain. Both cytokine and receptor deficient mice mount a robust CD8 T cell response to infection with lymphocytic choriomeningitis virus (LCMV) that is initially only slightly lower than in control mice. Further, virus specific memory CD8 T cells are generated in both IL-15 -/- and IL-15Ralpha -/- mice. However, longitudinal analysis reveals a slow attrition of LCMV specific memory CD8 T cells in the absence of IL-15 signals. Indeed, direct examination of homeostatic proliferation reveals a severe defect in the turnover of antigen specific memory CD8 T cells in the absence of IL-15. Together these results suggest that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.