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The Role Of Inhibitory Receptors With ITIM In Immunoregulation Of Organ Transplantation

Posted on:2009-10-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y B ZhaoFull Text:PDF
GTID:1114360242493761Subject:Urology
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[Objective] To investigate the role of inhibitory receptors with immunoreceptor tyrosine-based inhibition motif(ITIM) such as CD152 (cytotoxic T lymphocyte associated antigen-4, CTLA4), CD272 (B and T lymphocyte attenuator, BTLA), CD279 (programmed death-1, PD-1), CD305 (leukocyte-associated immunoglobulin-like receptor-1, LAIR-1) and CD306 (leukocyte-associated immunoglobulin-like receptor-2, LAIR-2) in immunoregulation of organ transplantation. [Methods] 1 .Heart transplantation model in cervix of mice were established. The allograft was from BalB/C to C57/BL6. The models were divided into 2 groups: acute rejection(AR) group and control group according to whether AR existed or not. The expression of mCD272 and mCD279 on the splenic lymphocyte were detected by FCM(flow cytometry). 2.sCD305 and CD306 in transplantation recipients' sera who were in different immune states such as kidney transplantation with AR group, DGF(delayed renal graft function) group, liver transplantation with AR group, regular hemodialysis/hemofiltration group, stable renal allograft function group were detected by ELISA. 3.sCD305 and CD306 in recipients who suffered from CMV(cytomegalovirus) pulmonitis following renal transplantation and who recovered smoothly(control group) were detected by ELISA. 4.mCD152 on the splenic lymphocyte of mice(the same grouping as 1) were detected by FCM. sCD152 in recipients'(the same grouping as 2) and normal human's sera were detected by ELISA. 5.The data were analyzed by Hest after mormal distribution were confirmed. [Results] 1.The POS ratio of CD272 in AR group of mice was (58.194±8.692)%(mean±SD), CD279 was (5.250±5.550)%. In control group, CD272 was (43.582±7.584)%, CD279 was in (0.390-67.750)%(nonnormal distribution). There was a significant difference of CD272 between 2 groups(P=0.0000) and no difference of CD279(P=0.0863). 2, sCD305 was in (0.854-54.415) ng/ml in regular hemodialysis/hemofiltration group, (0.000-5.942) ng/ml in stable renal allograft function group, (0.201-50.432) ng/ml in AR in renal transplantation group, (0.452-44.906) ng/ml in AR in liver transplantation group, (0.000-6.838) ng/ml in DGF group. CD306 was in (0.000-0.011) ng/ml in regular hemodialysis/hemofiltration group, (0.000-0.041) ng/ml in stable renal allograft function group, (0.002-0.045) ng/ml in AR in renal transplantation group, (0.000-0.042) ng/ml in AR in liver transplantation group, (0.001-0.085) ng/ml in DGF group. sCD305 in stable renal allograft function group was lower than the other 4 groups(P<0.05). sCD305 in regular hemodialysis/hemofiltration group was higher than the other 4 groups(P > 0.1). But CD306 had no difference between 5 groups(P > 0.05). 3.CD306 in CMV pulmonitis group was lower than control group(P=0.0002). sCD305 had no difference(P=0.3158). 4.CD152 had no difference between 2 groups in mice(P=0.4803). But CD 152 in stable renal allograft function group and AR in renal transplantation group were lower than DGF group and normal human(P < 0.05). [Conclusion] Inhibitory receptors with ITIM: CD152, CD272, CD279, CD305, CD306 play an important role in immunoloregulation. CD152, CD272 and CD279 express on T cell at different time. They produce a marked effect during the different phase of immune reaction. The expression of these 3 receptors will changed after transplantation according to uniform rule: there is a high expression in early stage and then considerable moleculars bind with ligands to downregulate immune reaction which caused a notable decreasing expression and at last the expression regain normal level. sCD305 play a major role in downregulating immune response. And CD306 can downregulate sLAIR-1 's function through competitive binding with their identical ligand. But only sCD305 can hint the harmful events after transplantation. The level of CD306 in serum maybe used as auxiliary diagnositic marker of CMV pneumonitis in renal transplantation recipient who has a stable graft function. Keywords: inhibitory receptor, ITIM motifs, organ transplantation...
Keywords/Search Tags:inhibitory receptor, ITIM motifs, organ transplantation
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