Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response.
T cell Ig mucin 3 (Tim-3) has been found to play an important role in Th1-mediated auto- and alloimmune responses, but the function of soluble form of Tim-3 (sTim-3) remains to be elucidated. In this study, we report the inhibitory effect of sTim-3 on T cell-mediated immune response. In this study, sTim-3 mRNA was found, among different tissues and organs, only in splenic cells, and the activation of splenocytes resulted in up-regulated production of both sTim-3 mRNA and protein. We constructed a eukaryotic expression plasmid, psTim-3, which expresses functional murine sTim-3. In C57BL/6 mice inoculated with B16F1 melanoma cells, the growth of tumor was facilitated by the expression of this plasmid in vivo. Furthermore, sTim-3 inhibited the responses of T cells to Ag-specific stimulation or anti-CD3 mAb plus anti-CD28 mAb costimulation and the production of cytokines IL-2 and IFN-gamma in vitro. In tumor rejection model, sTim-3 significantly impaired T cell antitumor immunity, evidenced by decreased antitumor CTL activity and reduced amount of tumor-infiltrating lymphocytes in tumor. Real-time PCR analysis of gene expression in tumor microenvironment revealed the decreased expression of Th1 cytokine genes and the unchanged profile of the genes related to T regulatory cell function, suggesting that the inhibitory effect of sTim-3 on the generation of Ag-specific T cells in vivo is dominated by T effector cells rather than T regulatory cells. Our studies thus define sTim-3 as an immunoregulatory molecule that may be involved in the negative regulation of T cell-mediated immune response.
Geng
Hui
H
Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, The People's Republic of China.
Zhang
Gui-Mei
GM
Li
Dong
D
Zhang
Hui
H
Yuan
Ye
Y
Zhu
Han-Gang
HG
Xiao
Han
H
Han
Ling-Fei
LF
Feng
Zuo-Hua
ZH
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands; D012333:RNA, Messenger; D011991:Receptors, Virus