title: Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population.
abstract: Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(-/-)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(-/-) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(-/-) allografts. Moreover, C3(-/-) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response.
authors.affiliation: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.|Department of Urology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Quan-You
authors.initials: QY
authors.lastname: Zheng
authors.affiliation: Department of Rheumatism and Immunology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Shen-Ju
authors.initials: SJ
authors.lastname: Liang
authors.affiliation: Department of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gui-Qing
authors.initials: GQ
authors.lastname: Li
authors.affiliation: Department of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Lv
authors.affiliation: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gui-Lian
authors.initials: GL
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D018925:Chemokines; D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit