title: Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells.
abstract: Impaired T-cell reactivity is a feature of C3-deficient mice in several disease models. The mechanism behind the reduced T-cell response is, however, poorly understood. We explored the hypothesis that antigen-presenting cells (APCs) from C3-/- mice have impaired potency to stimulate antigen-specific T cells, in an alloantigen-dependent model. Our results show that C3-/- macrophages have reduced ability to elicit alloreactive T-cell responses in vitro and in vivo, affecting both the primary and secondary responses. The C3 status of donor macrophages had a major impact on the CD4 T-cell response. The impaired CD4 T-cell response was associated with reduced expression of MHC class II on the surface of C3-/- macrophages, without loss of class II gene expression. Furthermore, inhibition of C3 gene expression in C3+/+ macrophages reduced their ability to stimulate alloreactive T cells, suggesting that endogenous production of C3 could in part contribute to the potency of APCs. Our data provide compelling evidence that C3 deficiency modulates the potency of APCs to stimulate the T-cell response, suggesting a critical role for complement in the maintenance of APC function. This could offer a partial explanation as to why the T-cell response is impaired in C3-/- mice.
authors.affiliation: Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's Hospital, London, SE1 9RT, United Kingdom. wuding.zhou@kcl.ac.uk
authors.forename: Wuding
authors.initials: W
authors.lastname: Zhou
authors.forename: Hetal
authors.initials: H
authors.lastname: Patel
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Villiers
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D003176:Complement C3; D000949:Histocompatibility Antigens Class II