CD8 alpha is expressed by human monocytes and enhances Fc gamma R-dependent responses.

CD8 alpha is expressed by human monocytes and enhances Fc gamma R-dependent responses.
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CD8α用人的单核细胞表达,并增强FCγ依赖性响应。

DOI:
10.1186/1471-2172-8-12
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发表时间:
2007-08-01
期刊:
影响因子:
3
通讯作者:
Befus, A. Dean
Befus, A. Dean
中科院分区:
医学4区
文献类型:
--
作者:
Gibbings, Derrick J.;Marcet-Palacios, Marcelo;Sekar, Yokananth;Ng, Marcus C. Y.;Befus, A. Dean

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CD8α通过结合MHC I类增强TCR激活的抗原特异性CTL的应答,有利于TCR的脂质筏分配,并诱导细胞内信号传导。在树突状细胞和大鼠巨噬细胞上也发现了CD8α,但CD8α是否增强了伙伴受体(如TCR)的反应,以激活这些细胞尚不清楚。TCR和FcR使用类似或偶尔可互换的信号机制,提示CD8α可能共同激活FcR反应。有趣的是,CD8α+单核细胞通常与大鼠疾病模型相关,包括免疫复合物沉积和fcr介导的病理,如关节炎、肾小球肾炎、缺血和肿瘤。而大鼠巨噬细胞已被证明表达CD8α,小鼠或人单核细胞或巨噬细胞表达CD8α的证据不完全。流式细胞术检测人单核细胞和单核细胞系THP-1的CD8α,未检测到CD8β。抗CD8α单抗与单核细胞的反应性至少部分独立于FcR,因为抗CD8α单抗通过western blot检测CD8α并抑制MHC I类四聚体的结合。CD8α mRNA也在单核细胞和THP-1中发现,这表明CD8α是由单核细胞合成的,而不是从其他CD8α+细胞类型获得的。有趣的是,来自单核细胞和血液T细胞的CD8α通过二维电泳呈现出可区分的模式。单独抗cd8α单抗不能激活单核细胞TNF释放。相比之下,在免疫复合物中加入抗cd8 α单抗后,以fcr依赖方式刺激的人单核细胞释放TNF增强。人单核细胞表达CD8α。CD8α和FcR的共同作用增强单核细胞TNF的释放,提示FcR可能是CD8α在先天免疫细胞上的一种新的伴侣受体。
CD8α enhances the responses of antigen-specific CTL activated through TCR through binding MHC class I, favoring lipid raft partitioning of TCR, and inducing intracellular signaling. CD8α is also found on dendritic cells and rat macrophages, but whether CD8α enhances responses of a partner receptor, like TCR, to activate these cells is not known. TCR and FcR, use analogous or occasionally interchangeable signaling mechanisms suggesting the possibility that CD8α co-activates FcR responses. Interestingly, CD8α+ monocytes are often associated with rat models of disease involving immune-complex deposition and FcR-mediated pathology, such as arthritis, glomerulonephritis, ischaemia, and tumors. While rat macrophages have been shown to express CD8α evidence for CD8α expression by mouse or human monocytes or macrophages was incomplete. We detected CD8α, but not CD8β on human monocytes and the monocytic cell line THP-1 by flow cytometry. Reactivity of anti-CD8α mAb with monocytes is at least partly independent of FcR as anti-CD8α mAb detect CD8α by western blot and inhibit binding of MHC class I tetramers. CD8α mRNA is also found in monocytes and THP-1 suggesting CD8α is synthesized by monocytes and not acquired from other CD8α+ cell types. Interestingly, CD8α from monocytes and blood T cells presented distinguishable patterns by 2-D electrophoresis. Anti-CD8α mAb alone did not activate monocyte TNF release. In comparison, TNF release by human monocytes stimulated in a FcR-dependent manner with immune-complexes was enhanced by inclusion of anti-CD8α mAb in immune-complexes. Human monocytes express CD8α. Co-engagement of CD8α and FcR enhances monocyte TNF release, suggesting FcR may be a novel partner receptor for CD8α on innate immune cells.
CD8BETA通过将T细胞受体/CD3与筏相关的CD8/p56(LCK)配合物耦合,使CD8具有有效的共感受器功能。
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