Overexpression of IL-15 in vivo increases antigen-driven memory CD8+ T cells following a microbe exposure

To elucidate potential roles of IL-15 in the maintenance of memory CD8(+) T cells, we followed the fate of Ag-specific CD8(+) T cells directly visualized with MHC class I tetramers coupled with listeriolysin O (LLO)(91-99) in IL-15 transgenic (Tg) mice after Listeria monocytogenes infection. The numbers of LLO91-99-positive memory CD8(+) T cells were significantly higher at 3 and 6 wk after infection than those in non-Tg mice. The LLO91-99-positive CD8(+) T cells produced IFN-gamma in response to LLO91-99, and an adoptive transfer of CD8(+) T cells from IL-15 Tg mice infected with L monocytogenes conferred a higher level of resistance against L. monocytogenes in normal mice. The CD44(+)CD8(+) T cells from infected IL-15 Tg mice expressed the higher level of Bcl-2. Transferred CD44(+)CD8(+) T cells divided more vigorously in naive IL-15 Tg mice than in non-Tg mice. These results suggest that IL-15 plays an important role in long-term maintenance of Ag-specific memory CD8(+) T cells following microbial exposure via promotion of cell survival and homeostatic proliferation.