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.
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