Wan Xiaoxiao, Unanue Emil R
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Precis Clin Med. 2018 Dec;1(3):102-110. doi: 10.1093/pcmedi/pby015. Epub 2018 Nov 23.
Development of human autoimmune disorders results from complex interplay among genetic, environmental, and immunological risk factors. Despite much heterogeneity in environmental triggers, the leading genes that give the propensity for tissue-specific autoimmune diseases, such as type 1 diabetes, are those associated with particular class II major histocompatibility complex alleles. Such genetic predisposition precipitates presentation of tissue antigens to MHC-II-restricted CD4 T cells. When properly activated, these self-reactive CD4 T cells migrate to the target tissue and trigger the initial immune attack. Using the non-obese diabetic mouse model of spontaneous autoimmune diabetes, much insight has been gained in understanding how presentation of physiological levels of self-antigens translates into pathological outcomes. In this review, we summarize recent advances illustrating the features of the antigen presenting cells, the sites of the antigen recognition, and the nature of the consequent T cell responses. We emphasize emerging evidence that highlights the importance of systemic presentation of catabolized tissue antigens in mobilization of pathogenic T cells. The implication of these studies in therapeutic perspectives is also discussed.
人类自身免疫性疾病的发生是遗传、环境和免疫风险因素之间复杂相互作用的结果。尽管环境触发因素存在很大异质性，但导致组织特异性自身免疫性疾病（如1型糖尿病）倾向的主要基因是那些与特定II类主要组织相容性复合体等位基因相关的基因。这种遗传易感性促使组织抗原呈递给MHC-II限制性CD4 T细胞。当被适当激活时，这些自身反应性CD4 T细胞迁移到靶组织并引发初始免疫攻击。利用自发性自身免疫性糖尿病的非肥胖糖尿病小鼠模型，我们在理解生理水平的自身抗原呈递如何转化为病理结果方面获得了很多见解。在这篇综述中，我们总结了最近的进展，阐述了抗原呈递细胞的特征、抗原识别位点以及随之而来的T细胞反应的性质。我们强调新出现的证据，这些证据突出了分解代谢组织抗原的全身呈递在致病性T细胞动员中的重要性。还讨论了这些研究在治疗前景方面的意义。
