Research ArticleIMMUNOLOGICAL MEMORY

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

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Science Immunology  13 Oct 2017:
Vol. 2, Issue 16, eaan6049
DOI: 10.1126/sciimmunol.aan6049

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Selecting memory T cells

Recruitment of immune cells to infected tissues relies on interactions between receptors on immune cells and adhesion molecules expressed by vascular endothelial cells, including E- and P-selectins. Here, Osborn et al. have compared the trafficking of effector and central memory T (TCM) cells and find that the ability to enter tissues is largely restricted to TCM cells. They found that interleukin-15–driven transcriptional programming of TCM cells promotes glycosylation of selectin ligands, allowing these cells to bind E- and P-selectins and to enter inflamed tissues. The studies represent a key advance in our understanding of how distinct memory T cell subsets contribute to recall responses.

Abstract

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 (TCM) 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 TCM CD8+ T cells, this allows TCM 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 TCM cells that have the capacity to synthesize core 2 O-glycans.

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