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

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.

journal_name

Immunity

journal_title

Immunity

authors

Smith LK,Boukhaled GM,Condotta SA,Mazouz S,Guthmiller JJ,Vijay R,Butler NS,Bruneau J,Shoukry NH,Krawczyk CM,Richer MJ

doi

10.1016/j.immuni.2018.01.006

subject

Has Abstract

pub_date

2018-02-20 00:00:00

pages

299-312.e5

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(18)30006-2

journal_volume

48

pub_type

杂志文章

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