title: Sirolimus-based regimen promotes inhibitory costimulatory signal of HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients.
abstract: HVEM/BTLA/CD160/LIGHT pathway is a very special costimulatory molecule system which can regulate T-cell immune responses by activating both inflammatory and inhibitory signalings. The regulatory effect of Sirolimus on HVME costimulatory system in allo-renal recipients has not been reported. In this study, we analyzed the expression of HVEM, BTLA, CD160 and LIGHT on circulating T cell subgroups and the expression of HVEM on CD4+ Tregs by flow cytometry and also the pre-dose concentration of Sirolimus by automatic analyzer. Both the allo-renal recipients receiving Sirolimus immunosuppressive regimen and health volunteers were included. The expression of both BTLA and CD160 on T cells increased significantly while the expression of LIGHT on T cells decreased significantly in allo-renal recipients receiving Sirolimus regimen (p<0.05). The expression of HVEM on T cells and CD4+ T-cell subgroup decreased (p<0.05) while that on CD8+ T-cell subgroup remained roughly normal (p>0.05).The expression of HVEM on CD4+ Tregs increased significantly (p<0.05) in allo-renal recipients receiving Sirolimus regimen (p<0.05). Though regulating the expression of HVEM/BTLA/CD160/LIGHT costimulatory system, Sirolimus-based regimen promotes inhibitory costimulatory signal in T cells and enhances the function of CD4+ Tregs in allo-renal recipients, which are in benefit of the control of transplant rejection as well as the induction and maintenance of transplant tolerance.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yangjuan
authors.initials: Y
authors.lastname: Bai
authors.forename: Yunying
authors.initials: Y
authors.lastname: Shi
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Bei
authors.initials: B
authors.lastname: Cai
authors.forename: Yuangao
authors.initials: Y
authors.lastname: Zou
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C482586:BTLA protein, human; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D020123:Sirolimus