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

doi:10.1016/j.immuni.2018.01.006

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

2018-02-01

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Stephanie A. Condotta

DOI：10.1016/j.immuni.2018.01.006

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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.

Keywords:

CHRONIC VIRAL-INFECTION

TUMOR-INFILTRATING LYMPHOCYTES

C VIRUS-INFECTION

HEPATITIS-C

IN-VIVO

IL-10

RECEPTOR

TCR

AVIDITY

PERSISTENCE

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

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