Up-regulation of Tim-3 expression contributes to development of burn-induced T cell immune suppression in mice.
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.
Department of Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangzh45@hotmail.com.
Zhaohui
Z
Tang
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Yan
Y
Yu
Department of Immunology, Medical College of Jianghan University, Wuhan, 430056, China.
Wenhong
W
Qiu
Department of Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Jian
J
Zhang
Lymphocyte Cell Biology Section, NIAMS, NIH, Bethesda, MD, 20892, USA.
Xiangping
X
Yang
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D007108:Immune Tolerance / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011991:Receptors, Virus / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation
D016207:Cytokines; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus