title: Local synthesis of complement component C3 regulates acute renal transplant rejection.
abstract: Accumulating evidence suggests that innate immunity interacts with the adaptive immune system to identify potentially harmful antigens and eliminate them from the host. A central facet of innate immunity is complement, which for some time has been recognized as a contributor to inflammation in transplant rejection but without detailed analysis of its role in what is principally a T cell mediated process. Moreover, epithelial and vascular tissues at local sites of inflammation secrete complement components; however, the role of such local synthesis remains unclear. Here we show that the absence of locally synthesized complement component C3 is capable of modulating the rejection of renal allografts in vivo and regulating T-cell responses in vivo and in vitro. The results indicate that improved success in kidney transplantation could come from therapeutic manipulation of innate immunity in concert with T cell directed immunosuppression.
authors.affiliation: Department of Nephrology & Transplantation, King's College University of London, Guy's Hospital, London, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Pratt
authors.forename: Shamim A
authors.initials: SA
authors.lastname: Basheer
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D006084:Graft Rejection / Q000473:pathology*; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D003176:Complement C3; D012333:RNA, Messenger