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

Jossef F Osborn; Jana L Mooster; Samuel J Hobbs; Michael W Munks; Conrad Barry; John T Harty; Ann B Hill; Jeffrey C Nolz

doi:10.1126/sciimmunol.aan6049

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

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

Jossef F Osborn, Jana L Mooster, Samuel J Hobbs, Michael W Munks, Conrad Barry, John T Harty, Ann B Hill and Jeffrey C Nolz

Science immunology, Vol.2(16), p.eaan6049

10/13/2017

DOI: 10.1126/sciimmunol.aan6049

PMCID: PMC5786265

PMID: 29030501

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

Lymphocytic choriomeningitis virus - immunology

Cytoplasm - virology

Inflammation

Polysaccharides - immunology

Interleukin-15 - immunology

Polysaccharides - biosynthesis

CD8-Positive T-Lymphocytes - enzymology

Animals

Interleukin-15 - genetics

Cytoplasm - immunology

Immunologic Memory

Mice

CD8-Positive T-Lymphocytes - immunology

Cell Movement

Details

Title: Subtitle: Enzymatic synthesis of core 2 O-glycans governs the tissue-trafficking potential of memory CD8 + T cells
Creators: Jossef F Osborn - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Jana L Mooster - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Samuel J Hobbs - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Michael W Munks - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Conrad Barry - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
John T Harty - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Ann B Hill - Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Jeffrey C Nolz - Department of Radiation Medicine, Oregon Health and Science University, Portland, OR 97239, USA
Resource Type: Journal article
Publication Details: Science immunology, Vol.2(16), p.eaan6049
DOI: 10.1126/sciimmunol.aan6049
PMID: 29030501
PMCID: PMC5786265
NLM abbreviation: Sci Immunol
ISSN: 2470-9468
eISSN: 2470-9468
Publisher: United States
Grant note: R01 AI047206 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS R01 AI132404 / NIAID NIH HHS K22 AI102981 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 10/13/2017
Academic Unit: Pathology
Record Identifier: 9984046918502771

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