[Expression of Tim-3 in tumor tissue and its role in the induction of tumor immune tolerance].
OBJECTIVE
To explore the role of T cell immunoglobulin- and mucin- domain containing molecule-3 (Tim-3) in the induction of tumor immune tolerance by investigating the expression of two types of Tim-3 at the early stage of tumorigenesis and the temporal-spatial relationship between the expression of Tim-3 and other immuno-inhibitory genes in tumor.


METHODS
By using semi-quantitative RT-PCR method, we investigated the expression of Tim-3, forkhead box P3 (Foxp3), cytotoxic T lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR), TGF-beta, IL-10 and IFN-gamma at different time in tumor of tumor-bearing mice. Meanwhile, the growth of tumor was determined.


RESULTS
At the early stage of tumorigenesis, sTim-3 was expressed before flTim-3 in tumor. When flTim-3 was expressed, the expression of sTim-3 was down-regulated. The expression of Foxp3, and GITR was simultaneous with that of flTim-3 and was up-regulated gradually with tumor growth. The expression of CTLA-4 was earlier than that of flTim-3 and also up-regulated gradually. The expression of flTim-3 and Foxp3 was also consistent with each other in tissue distribution. The growth of tumor was postively correlated with the expression of flTim-3, Foxp3, and CTLA-4 and negatively with the expression of sTim-3.


CONCLUSIONS
Along with the growth of tumor, immune tolerance was gradually established in tumor. flTim-3 but not sTim-3 may induce tumor immunological tolerance.
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China. hg2zhu@126.com
Han-gang
HG
Zhu
Zuo-hua
ZH
Feng
Hui
H
Geng
Gui-mei
GM
Zhang
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000235:genetics
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma