IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors

Immunohorizons. 2019 Jan 15;3(1):13-25. doi: 10.4049/immunohorizons.1800083.

Abstract

Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T cell activation, but there are gaps in our knowledge of the cell-extrinsic factors that regulate their expression. The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expression of PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted expression of multiple IRs, whereas IL-27 alone induced expression of PD-L1. However, the combination of intermediate TCR stimulation and IL-27 resulted in synergistic induction of LAG-3, CTLA-4, and TIGIT. In vivo, infection with Toxoplasma gondii resulted in parasite-specific effector T cells that expressed high levels of IR, and at local sites of infection where IL-27 production was highest, IL-27 was required for maximal effector cell expression of PD-L1, LAG-3, CTLA-4, and TIGIT. Together, these results affirm the critical role of TCR signals in the induction of IR expression but find that during infection, IL-27 promotes T cell expression of IR.

Publication types

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

MeSH terms

  • Animals
  • B7-H1 Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / parasitology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / parasitology
  • CTLA-4 Antigen / metabolism
  • Costimulatory and Inhibitory T-Cell Receptors / genetics
  • Costimulatory and Inhibitory T-Cell Receptors / metabolism*
  • Female
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Immunologic / metabolism
  • Spleen / pathology
  • Toxoplasma
  • Toxoplasmosis / immunology
  • Transcriptome
  • Transfection

Substances

  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Cd274 protein, mouse
  • Costimulatory and Inhibitory T-Cell Receptors
  • Interleukins
  • MYDGF protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • T cell Ig and ITIM domain protein, mouse