title: IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking.
abstract: Memory and naive CD8+ T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8+ T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8+ T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8+ T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues. Following infection, antigen-specific effector CD8+ T cells strongly expressed core 2 O-glycans, but this glycosylation pattern was lost by most memory CD8+ T cells. After unrelated infection or inflammatory challenge, memory CD8+ T cells synthesized core 2 O-glycans independently of antigen restimulation. The presence of core 2 O-glycans subsequently directed these cells to inflamed tissue. Memory and naive CD8+ T cells exhibited the opposite pattern of epigenetic modifications at the Gcnt1 locus, which encodes the enzyme that initiates core 2 O-glycan synthesis. The open chromatin configuration in memory CD8+ T cells permitted de novo generation of core 2 O-glycans in a TCR-independent, but IL-15-dependent, manner. Thus, IL-15 stimulation promotes antigen-experienced memory CD8+ T cells to generate core 2 O-glycans, which subsequently localize them to inflamed tissues. These findings suggest that CD8+ memory T cell trafficking potentially can be manipulated to improve host defense and immunotherapy.
authors: Jeffrey C
authors: JC
authors: Nolz
authors: John T
authors: JT
authors: Harty
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D019040:E-Selectin / Q000378:metabolism; D006031:Glycosylation; D007156:Immunologic Memory; D007249:Inflammation; D019409:Interleukin-15 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000821:virology; D012867:Skin / Q000276:immunology / Q000821:virology; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D019040:E-Selectin; D019409:Interleukin-15; D008070:Lipopolysaccharides; D019007:P-Selectin; D011134:Polysaccharides; D051193:Toll-Like Receptors; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase