Up-regulation of Tim-3 Expression Contributes to Development of Burn-induced T Cell Immune Suppression in Mice

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 31; no. 5; pp. 642 - 651
• Main Author: 唐朝晖 余彦 邱文洪 张剑 杨想平
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.10.2011; Department of Trauma Surgery%Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China%Department of Immunology, Medical College of Jianghan University, Wuhan 430056, China%Lymphocyte Cell Biology Section, NIAMS, NIH, Bethesda, MD, 20892, USA
• Subjects: Animals; Apoptosis; Burns; Burns - immunology; Burns - metabolism; CD4 antigen; CD8 antigen; Cell proliferation; Cytokines - immunology; gamma -Interferon; Hepatitis A Virus Cellular Receptor 2; Immune Tolerance - immunology; Immunoglobulins; Inflammation; Injuries; Interleukin 10; Liver; Lymphocytes T; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; mucin; PD-1 protein; Receptors, Virus - metabolism; Spleen; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; TIM; Tumor necrosis factor- alpha; T细胞亚群; Up-Regulation; 体内; 免疫抑制; 小鼠; 炎性细胞因子; 烧伤; 诱导; burn injury; T cells; immune suppression; T cell immunoglobulin and mucin domain 3; bum injury
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-011-0575-0

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.