title: Complement regulation of T-cell alloimmunity.
abstract: OBJECTIVE
  The purpose of this review is to summarize recent findings implicating complement as an important regulator of T-cell immune responses. We then provide perspective for how these newly described mechanisms apply to allograft injury and how they could ultimately influence therapy.
  
  
  RESULTS
  In addition to known effects of serum complement as an effector arm of antibody-initiated injury, T cells and antigen-presenting cells produce complement proteins and up-regulate complement receptors following cognate interactions. The locally released and activated, immune cell-derived complement signals predominantly through C3a and C5a binding to their receptors expressed on both partners to induce immune cell activation and differentiation. Complement deficiency or blockade limits T-cell-mediated autoimmunity and transplant rejection, whereas removal of the complement regulatory protein decay accelerating factor can enhance T-cell immunity and accelerate graft rejection.
  
  
  CONCLUSIONS
  Emerging data indicate that immune cell-derived complement physiologically regulates immune cell survival and proliferation, modulating the strength and phenotype of adaptive T-cell immune responses involved in transplant rejection. The recognition of the diversity through which complement participates in allograft injury supports the need for continued design and testing of complement inhibitors in human transplant recipients.
authors.affiliation: Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Hugo
authors.initials: H
authors.lastname: Raedler
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology
chemical_list: D003165:Complement System Proteins