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

Immunity. 2018 Feb 20;48(2):299-312.e5. doi: 10.1016/j.immuni.2018.01.006. Epub 2018 Jan 23.

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.

Keywords: CD8(+) T cells; Mgat5; antigen sensitivity; chronic infection; galectin 3; glycosylation; immune regulation; interleukin 10.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Galectins / physiology
  • Glycosylation
  • Interleukin-10 / physiology*
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • N-Acetylglucosaminyltransferases / physiology
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / physiology

Substances

  • Antigens, Viral
  • Galectins
  • Receptors, Antigen, T-Cell
  • Interleukin-10
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase