Activation of Tim-3-Galectin-9 pathway improves survival of fully allogeneic skin grafts.
T cell immunoglobulin and mucin domain (Tim)-3 is a molecule expressed on terminally differentiated murine Th1 cells but not on Th2 cells. Identification of Galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3-Galectin-9 pathway as an important regulator of Th1 immunity, which results in apoptosis of Th1 cells. Here, we demonstrate that engagement of Tim-3 by mouse recombinant Galectin-9 remarkably suppresses allograft rejection and improves survival of allogeneic skin grafts. Furthermore, administration of recombinant Galectin-9 decreases Tim-3 positive cells in draining lymph node and selectively inhibits production of IFN-gamma after skin transplantation. At last, even low dose of Galectin-9 (1 microg/ml) can obviously inhibit TCR crosslinking-induced primary T cell proliferation in vitro. These observations suggest that Tim-3-Galectin-9 pathway plays an important role in the termination of productive Th1-immune response and could lead to developing novel therapies in transplant medicine.
Wang
Feng
F
Institute of Organ Transplantation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
He
Wentao
W
Yuan
Jin
J
Wu
Ke
K
Zhou
Hongmin
H
Zhang
Weina
W
Chen
Zhonghua Klaus
ZK
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D037161:Galectins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016038:Skin Transplantation / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011948:Receptors, Antigen, T-Cell; D011991:Receptors, Virus; D011994:Recombinant Proteins; C508186:galectin 9, mouse; D007371:Interferon-gamma