L-selectin Is Essential for Delivery of Activated CD8+ T Cells to Virus-Infected Organs for Protective Immunity

Cytotoxic CD8+ T lymphocytes play a critical role in the host response to infection by viruses. The ability to secrete cytotoxic chemicals and cytokines is considered pivotal for eliminating virus. Of equal importance is how effector CD8+ T cells home to virus-infected tissues. L-selectin has not been considered important for effector T cell homing, because levels are low on activated T cells. We report here that, although L-selectin expression is downregulated following T cell priming in lymph nodes, L-selectin is re-expressed on activated CD8+ T cells entering the bloodstream, and recruitment of activated CD8+ T cells from the bloodstream into virus-infected tissues is L-selectin dependent. Furthermore, L-selectin on effector CD8+ T cells confers protective immunity to two evolutionally distinct viruses, vaccinia and influenza, which infect mucosal and visceral organs, respectively. These results connect homing and a function of virus-specific CD8+ T cells to a single molecule, L-selectin. [Display omitted] •L-selectin is re-expressed on activated CD8+ T cells exiting lymph nodes•L-selectin does not regulate priming, differentiation, or function of cytotoxic T lymphocytes•Entry of activated CD8+ T cells into virus-infected tissues is L-selectin dependent•The level of cell-surface L-selectin determines the extent of anti-viral immunity Lymphocyte migration is a key step in the host’s immune response against viruses. Mohammed et al. demonstrate that re-expressed L-selectin/CD62L on primed virus-specific CD8+ T cells plays a pivotal role in their recruitment from the bloodstream into virus-infected tissues for protective immunity.