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金过敏中,金特异性T细胞与抗原呈递细胞之间的杂乱相互作用。

Promiscuous interaction between gold-specific T cells and APCs in gold allergy.

作者信息

Hashizume Hideo, Seo Naohiro, Ito Taisuke, Takigawa Masahiro, Yagi Hiroaki

机构信息

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

J Immunol. 2008 Dec 1;181(11):8096-102. doi: 10.4049/jimmunol.181.11.8096.

Abstract

Gold compounds clinically used as immunomodulators have high potential to evoke hypersensitivity reactions as an adverse effect. To explore the mechanism of gold allergy, we immunologically characterized T cells infiltrating skin rashes and generated 44 gold-specific T cell clones and lines from a rheumatoid arthritis patient who developed skin rashes and systemic symptoms after gold treatment. CD4(+) and CD8(+) cells predominantly infiltrating the skin rashes and some of the T cell clones and lines shared common Vbetas. These cells exhibited Th0-like, Th2-like, and Tc1-like cytokine profiles, and showed chemotactic activities for thymus and activation-regulated chemokine and IFN-gamma-inducible protein-10 corresponding to the cytokine profiles. T cell recognition of gold consisted of MHC-restricted and MHC-independent pathways. Blocking studies with anti-MHC Abs indicated that the groove of MHC in APCs, where Ags should ordinarily be settled, did not serve as a conjugating site of gold for these T cells in certain cases. These observations raise the possibility that gold-specific CD4(+) and CD8(+) T cells and APCs promiscuously interact under stimulation with gold, resulting in various clinical manifestations in gold allergy.

摘要

临床上用作免疫调节剂的金化合物具有引发超敏反应作为不良反应的高潜力。为了探究金过敏的机制,我们对浸润皮疹的T细胞进行了免疫学特征分析,并从一名在金治疗后出现皮疹和全身症状的类风湿性关节炎患者中产生了44个金特异性T细胞克隆和细胞系。主要浸润皮疹的CD4(+)和CD8(+)细胞以及一些T细胞克隆和细胞系共享共同的Vβ。这些细胞表现出类似Th0、Th2和Tc1的细胞因子谱,并对胸腺和活化调节趋化因子以及与细胞因子谱相对应的IFN-γ诱导蛋白-10表现出趋化活性。T细胞对金的识别由MHC限制和MHC非依赖途径组成。用抗MHC抗体进行的阻断研究表明,在某些情况下,抗原呈递细胞(APC)中通常应容纳抗原的MHC凹槽并不是这些T细胞的金结合位点。这些观察结果增加了一种可能性,即金特异性CD4(+)和CD8(+) T细胞与APC在金刺激下发生混杂相互作用,从而导致金过敏的各种临床表现。

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