Enzymatic synthesis of core 2 O-glycans governs the tissue-trafficking potential of memory CD8⁺ T cells

Trafficking of memory CD8⁺ T cells out of the circulation is essential to provide protective immunity against intracellular pathogens in nonlymphoid tissues. However, the molecular mechanisms that dictate the trafficking potential of diverse memory CD8⁺ T cell populations are not completely defined. We show that after infection or inflammatory challenge, central memory (T_CM) CD8⁺ T cells rapidly traffic into nonlymphoid tissues, whereas most effector memory cells remain in the circulation. Furthermore, we demonstrate that cellular migration of memory CD8⁺ T cells into nonlymphoid tissues is driven by interleukin-15 (IL-15)–stimulated enzymatic synthesis of core 2 O-glycans, which generates functional ligands for E- and P-selectins. Given that IL-15–stimulated expression of glycosyltransferase enzymes is largely a feature of T_CM CD8⁺ T cells, this allows T_CM to selectively migrate out of the circulation and into nonlymphoid tissues. Collectively, our data indicate that entry of memory CD8⁺ T cells into inflamed, nonlymphoid tissues is primarily restricted to T_CM cells that have the capacity to synthesize core 2 O-glycans.