The Tim-3 ligand galectin-9 negatively regulates CD8+ alloreactive T cell and prolongs survival of skin graft.
CD8+ alloreactive T cells are the key mediators of accelerated rejection. Vigorous CD8+ alloreactive T cells responses against alloantigens, which is the main effector mechanism in acute allograft rejection, has been well described. But the molecular mechanisms to dampen activated CD8+ T cells are largely unknown. On the other hand, Tim-3 is a molecule expressed on terminally differentiated CD4+ Th1 cells. Engaging Tim-3 with its ligand galectin-9 causes an inhibitory signal, resulting in apoptosis of Th1 cells and negatively regulates Th1 type immunity. However, the question whether CD8+ T cells express surface molecular Tim-3 has not been fully elucidated. In this study, we have investigated which CD8+ subset express molecular Tim-3 by flow cytometric assay. In addition, cytotoxic assay was applied to analyze whether CD8+ alloreactive T cells were sensitive to galectin-9 induced apoptosis. Here, our results demonstrated that Tim-3 was expressed on activated CD8+ alloreactive T cells (CD8+CD44highCD62Llow), but not expressed on naïve CD8+ T cells. Furthermore, alloreactive CD8+ cytotoxic T cells were sensitive to galectin-9 induced apoptosis both in vitro and vivo, resulting in attenuation of CD8+ alloreactive T cells mediated cytotoxicity and prolonged survival of skin graft.
Wang
Feng
F
Institute of Organ Transplantation, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, 1095 Jiefang Road, Wuhan, Hubei 430030, China.
He
Wentao
W
Zhou
Hongmin
H
Yuan
Jin
J
Wu
Ke
K
Xu
Lijun
L
Chen
Zhonghua Klaus
ZK
D000818:Animals; D017209:Apoptosis; D004797:Enzyme-Linked Immunosorbent Assay; D037161:Galectins / Q000494:pharmacology / Q000502:physiology*; D006085:Graft Survival / Q000187:drug effects*; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011991:Receptors, Virus / Q000008:administration & dosage*; D016038:Skin Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands; D011991:Receptors, Virus; D007371:Interferon-gamma