Journal
IMMUNITY
Volume 48, Issue 2, Pages 299-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.01.006
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Funding
- McGill Faculty of Medicine
- NSERC [RGPIN-2016-04713]
- FRQS [32807]
- CIHR [PJT-152903, MOP-126184, MOP-133680]
- NIH/NIAID [R01AI125446, R01AI127481]
- FRQS AIDS and Infectious Disease Network (Reseau SIDA-MI)
- CIHR
- FRQS
- Canadian Network on Hepatitis C (CanHepC)
- joint initiative of the CIHR [NHC-142832]
- Public Health Agency of Canada
- Alberta Innovates [201201140] Funding Source: researchfish
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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.
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