Alpha beta-crystallin expression and presentation following infection with murine gammaherpesvirus 68.
Alpha beta-crystallin expression and presentation following infection with murine gammaherpesvirus 68.
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DOI：
10.3109/08916934.2013.785535
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发表时间：
2013-09
期刊：
影响因子：
3.5
通讯作者：
Bost KL
中科院分区：
文献类型：
--
作者：
Chauhan VS;Nelson DA;Marriott I;Bost KL
α-β-晶状体蛋白（α-β-crystallin，α-β-crystallin AB）是一种小的热休克蛋白，可以作为分子伴侣发挥作用，对经历各种应激源的细胞具有保护作用。令人惊讶的是，已鉴定为多发性硬化症中的主要自身抗原之一。有人认为，这种小的热休克蛋白的自身免疫介导的破坏可能会限制其保护作用，从而加剧多发性硬化症期间的炎症和细胞损伤。目前还不完全清楚抗CD 4AB的自身免疫是如何发展的，或者是否有环境因素可能促进这种自身抗原呈递给CD 4 + T淋巴细胞。在本研究中，我们利用了一个动物模型的爱泼斯坦巴尔病毒（EBV）样感染，鼠γ疱疹病毒68（HV-68），以质疑这种病毒是否可以调节抗原呈递细胞的表达的ESTAB。暴露于HV-68和其他几种刺激物后，在培养的巨噬细胞和树突状细胞中观察到体外分泌的TGF-AB和随后的细胞内积累。在用该病毒感染小鼠后，可以追踪脾脏和抗原呈递细胞亚群中的HSP 7AB表达，以及其分泌到血液中。用人HSP 7AB免疫的小鼠对这种热休克蛋白产生了显著的免疫应答。此外，暴露于HV-68的树突状细胞可以刺激来自HLA-AB免疫小鼠的CD 4 + T细胞分泌干扰素γ。总之，这些研究与在该小鼠模型中的专职抗原呈递细胞中γ疱疹病毒诱导的ESTAB应答的概念一致。
Alpha beta-crystallin (CRYAB) is a small heat shock protein that can function as a molecular chaperone and has protective effects for cells undergoing a variety of stressors. Surprisingly, CRYAB has been identified as one of the dominant autoantigens in multiple sclerosis. It has been suggested that autoimmune mediated destruction of this small heat shock protein may limit its protective effects, thereby exacerbating inflammation and cellular damage during multiple sclerosis. It is not altogether clear how autoimmunity against CRYAB might develop, or whether there are environmental factors which might facilitate the presentation of this autoantigen to CD4+ T lymphocytes. In the present study, we utilized an animal model of an Epstein Barr Virus (EBV)-like infection, murine gammaherpesvirus 68 (HV-68), to question whether such a virus could modulate the expression of CRYAB by antigen presenting cells. Following exposure to HV-68 and several other stimuli, in vitro secretion of CRYAB and subsequent intracellular accumulation were observed in cultured macrophages and dendritic cells. Following infection of mice with this virus, it was possible to track CRYAB expression in the spleen and in antigen presenting cell subpopulations, as well as its secretion into the blood. Mice immunized with human CRYAB mounted a significant immune response against this heat shock protein. Further, dendritic cells that were exposed to HV-68 could stimulate CD4+ T cells from CRYAB immunized mice to secrete interferon gamma. Taken together these studies are consistent with the notion of a gammaherpesvirus-induced CRYAB response in professional antigen presenting cells in this mouse model.
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影响因子：
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作者：
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