Cutting Edge: IL-15–Independent Maintenance of Mucosally Generated Memory CD8 T Cells

Effective vaccines against intracellular pathogens rely on the generation and maintenance of memory CD8 T cells (T(mem)). Hitherto, evidence has indicated that CD8 T(mem) use the common γ-chain cytokine IL-15 for their steady-state maintenance in the absence of Ag. This evidence, however, has been amassed predominantly from models of acute, systemic infections. Given that the route of infection can have significant impact on the quantity and quality of the resultant T(mem), reliance on limited models of infection may restrict our understanding of long-term CD8 T(mem) survival. In this article, we show IL-15-independent generation, maintenance, and function of CD8 T(mem) after respiratory infection with influenza virus. Importantly, we demonstrate that alternating between mucosal and systemic deliveries of the identical virus prompts this change in IL-15 dependence, necessitating a re-evaluation of the current model of CD8 T(mem) maintenance.