Up-regulation of Tim-3 expression contributes to development of burn-induced T cell immune suppression in mice

J Huazhong Univ Sci Technolog Med Sci. 2011 Oct;31(5):642. doi: 10.1007/s11596-011-0575-0. Epub 2011 Oct 25.

Abstract

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3(+) T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4(+) and CD8(+) T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3(+) T cells subsets were more prone to spontaneous apoptosis than Tim-3(-) T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns / immunology*
  • Burns / metabolism
  • Cytokines / immunology
  • Hepatitis A Virus Cellular Receptor 2
  • Immune Tolerance / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Virus / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Up-Regulation

Substances

  • Cytokines
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Receptors, Virus