Complement regulation of T cell immunity
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Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell–derived, alternative pathway complement components activate spontaneously, yielding local, but not systemic, production of C3a and C5a. These anaphylatoxins bind to their respective G-protein-coupled receptors, C3aR and C5aR, expressed on both partners. The resultant complement-induced T cell activation and APC activation drive T cell differentiation, expansion and survival. Complement deficiency or blockade attenuates T cell-mediated autoimmunity and delays allograft rejection in mice. Increasing complement activation, achieved by genetic removal of the complement regulatory protein decay-accelerating factor, enhances murine T cell immunity and accelerates allograft rejection. The findings support the need for design and testing of complement inhibitors in humans.
KeywordsT cells Allograft rejection Complement Costimulation Autoimmunity
This work was supported by NIH grants AI43578 and AI071185 to PSH. WK is a recipient of a fellowship grant from the American Society of Transplantation.
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