Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Mount Sinai School of Medicine, Box 1243, One Gustave L. Levy Plaza, New York, NY 10029, USA.
Immunol Res. 2012 Dec;54(1-3):247-53. doi: 10.1007/s12026-012-8327-1.
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.
自 2002 年以来发表的研究结果表明，T 细胞和抗原呈递细胞（APCs）会产生补体蛋白。免疫细胞衍生的替代途径补体成分会自动激活，导致局部而非全身产生 C3a 和 C5a。这些过敏毒素与各自的 G 蛋白偶联受体 C3aR 和 C5aR 结合，这些受体在两者中均有表达。由此产生的补体诱导的 T 细胞激活和 APC 激活驱动 T 细胞分化、扩增和存活。补体缺陷或阻断会减弱 T 细胞介导的自身免疫，并延迟小鼠同种异体移植物排斥。通过遗传去除补体调节蛋白衰变加速因子来增加补体激活，可增强小鼠的 T 细胞免疫并加速同种异体移植物排斥。这些发现支持在人类中设计和测试补体抑制剂的必要性。
