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

Sci Immunol. 2017 Oct 13;2(16):eaan6049. doi: 10.1126/sciimmunol.aan6049.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Cytoplasm / immunology
  • Cytoplasm / virology
  • Immunologic Memory*
  • Inflammation
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Polysaccharides / biosynthesis
  • Polysaccharides / immunology*

Substances

  • Interleukin-15
  • Polysaccharides