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 LLO_91-99-positive memory CD8⁺ T cells were significantly higher at 3 and 6 wk after infection than those in non-Tg mice. The LLO_91-99-positive CD8⁺ T cells produced IFN-γ in response to LLO_91-99, 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.