Complement regulation of T-cell alloimmunity.
Complement regulation of T-cell alloimmunity.
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DOI：
10.1016/j.semnephrol.2013.08.007
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发表时间：
2013-11
影响因子：
3.3
通讯作者：
Heeger, Peter S.
中科院分区：
文献类型：
--
作者：
Cravedi, Paolo;van der Touw, William;Heeger, Peter S.
补体蛋白由肝脏（全身细胞室）和外周组织驻留细胞和迁移免疫细胞（局部细胞室）产生。免疫细胞衍生的替代途径补体成分自发激活，产生局部而非全身的C3a和C5a。这些过敏毒素结合各自的g蛋白偶联受体，C3a受体和C5a受体，在T细胞和抗原呈递细胞上表达，导致它们的相互激活并驱动T细胞分化、扩增和存活。补体缺乏或阻断可减弱小鼠t细胞介导的自身免疫并延缓同种异体移植排斥反应。通过基因去除补体调节蛋白衰变加速因子来增加补体激活，增强小鼠t细胞免疫并加速同种异体移植排斥反应。通过C3a受体和C5a受体的信号传导降低了天然调节性T细胞的抑制活性以及诱导调节性T细胞的生成和稳定性。这些概念最初是在小鼠身上产生的，最近在人类免疫细胞中得到了证实，这支持了在器官移植患者身上测试补体靶向疗法的必要性。
Complement proteins are generated both by the liver (systemic compartment) and by peripheral tissue-resident cells and migratory immune cells (local compartment). 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, the C3a receptor and the C5a receptor, expressed on T cells and antigen-presenting cells, leading to their reciprocal activation and driving 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. Signaling through the C3a receptor and the C5a receptor reduces suppressive activity of natural regulatory T cells and the generation and stability of induced regulatory T cells. The concepts, initially generated in mice, recently were confirmed in human immune cells, supporting the need for testing of complement targeting therapies in organ transplants patients.
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DOI：
10.1084/jem.20041967
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heeger PS;Lalli PN;Lin F;Valujskikh A;Liu J;Muqim N;Xu Y;Medof ME
通讯作者：
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影响因子：
4.4
作者：
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Medof, M. Edward
影响因子：
20.3
作者：
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通讯作者：
Heeger, Peter S.
影响因子：
15.9
作者：
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通讯作者：
Heeger, Peter S.
DOI：
10.1016/j.trre.2010.04.002
发表时间：
2010-07
期刊：
Transplantation reviews (Orlando, Fla.)
影响因子：
--
作者：
Gorantla VS;Schneeberger S;Brandacher G;Sucher R;Zhang D;Lee WP;Zheng XX
通讯作者：
Zheng XX