Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype.
Previous studies have found that deficiency of complement component C3 is associated with reduced T cell responses in several disease models including viral infection, autoimmune disease, and transplantation. However, the underlying mechanism is unclear. In this study, we demonstrate that dendritic cells (DCs) are able to synthesize C3 and this synthesis is required for the capacity of DCs to stimulate alloreactive T cell responses in vitro and in vivo. Compared with C3-producing DCs, C3-nonproducing DCs exhibit reduced potency to stimulate an alloreactive T cell response, favor the polarization of CD4(+) T cells toward Th2 phenotype, and have regulatory T cell-driving capacity. In addition, priming mice with C3-deficient DCs compared with wild-type DCs led to delayed skin allograft rejection. Our findings that nonproduction of C3 by DCs significantly reduced T cell stimulation and impaired allograft rejection provide a potentially important explanation of how C3-deficient mice develop reduced T cell responses and of how C3-deficient donor kidney is protected from T cell-mediated graft rejection.
Peng
Qi
Q
Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's, King's College and St. Thomas' Hospitals, London SE1 9RT, United Kingdom.
Li
Ke
K
Patel
Hetal
H
Sacks
Steven H
SH
Zhou
Wuding
W
D000818:Animals; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering