Interleukin-10 Directly Inhibits CD8 + T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity

Logan K Smith; Giselle M Boukhaled; Stephanie A Condotta; Sabrina Mazouz; Jenna J Guthmiller; Rahul Vijay; Noah S Butler; Julie Bruneau; Naglaa H Shoukry; Connie M Krawczyk; Martin J Richer

doi:10.1016/j.immuni.2018.01.006

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Interleukin-10 Directly Inhibits CD8 + T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity

Journal article

Open access

Peer reviewed

Interleukin-10 Directly Inhibits CD8 + T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity

Logan K Smith, Giselle M Boukhaled, Stephanie A Condotta, Sabrina Mazouz, Jenna J Guthmiller, Rahul Vijay, Noah S Butler, Julie Bruneau, Naglaa H Shoukry, Connie M Krawczyk, …

Immunity (Cambridge, Mass.), Vol.48(2), pp.299-312.e5

02/20/2018

DOI: 10.1016/j.immuni.2018.01.006

PMCID: PMC5935130

PMID: 29396160

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Abstract

Chronic viral infections remain a global health concern. The early events that facilitate viral persistence have been linked to the activity of the immunoregulatory cytokine IL-10. However, the mechanisms by which IL-10 facilitates the establishment of chronic infection are not fully understood. Herein, we demonstrated that the antigen sensitivity of CD8 T cells was decreased during chronic infection and that this was directly mediated by IL-10. Mechanistically, we showed that IL-10 induced the expression of Mgat5, a glycosyltransferase that enhances N-glycan branching on surface glycoproteins. Increased N-glycan branching on CD8 T cells promoted the formation of a galectin 3-mediated membrane lattice, which restricted the interaction of key glycoproteins, ultimately increasing the antigenic threshold required for T cell activation. Our study identified a regulatory loop in which IL-10 directly restricts CD8 T cell activation and function through modification of cell surface glycosylation allowing the establishment of chronic infection.

Lymphocytic choriomeningitis virus - immunology

Mice, Inbred C57BL

Male

Glycosylation

Interleukin-10 - physiology

Receptors, Antigen, T-Cell - physiology

Antigens, Viral - immunology

Animals

Galectins - physiology

N-Acetylglucosaminyltransferases - physiology

Female

Signal Transduction - physiology

Mice

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: Interleukin-10 Directly Inhibits CD8 + T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity
Creators: Logan K Smith - Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Microbiome and Disease Tolerance Centre, McGill University, Montreal, QC, Canada
Giselle M Boukhaled - Department of Physiology, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada
Stephanie A Condotta - Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Microbiome and Disease Tolerance Centre, McGill University, Montreal, QC, Canada
Sabrina Mazouz - Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada; Department of Microbiology, Immunology and Infectiology, Université de Montréal, Montreal, QC, Canada
Jenna J Guthmiller - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Rahul Vijay - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA
Noah S Butler - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA
Julie Bruneau - Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada; Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, QC, Canada
Naglaa H Shoukry - Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada; Department of Medicine, Université de Montréal, Montreal, QC, Canada
Connie M Krawczyk - Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Department of Physiology, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada
Martin J Richer - Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Microbiome and Disease Tolerance Centre, McGill University, Montreal, QC, Canada. Electronic address: martin.j.richer@mcgill.ca
Resource Type: Journal article
Publication Details: Immunity (Cambridge, Mass.), Vol.48(2), pp.299-312.e5
Publisher: United States
DOI: 10.1016/j.immuni.2018.01.006
PMID: 29396160
PMCID: PMC5935130
ISSN: 1074-7613
eISSN: 1097-4180
Grant note: MOP-133680 / CIHR NHC-142832 / CIHR PJT-152903 / CIHR R01 AI127481 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R01 AI125446 / NIAID NIH HHS MOP-126184 / CIHR
Language: English
Date published: 02/20/2018
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001123002771

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