Chen Lina, Duvvuri Bhargavi, Grigull Jörg, Jamnik Roni, Wither Joan E, Wu Gillian E
Department of Kinesiology and Health Science, York University, Canada.
Department of Kinesiology and Health Science, York University, Canada.
Hum Immunol. 2014 Aug;75(8):873-9. doi: 10.1016/j.humimm.2014.06.012. Epub 2014 Jun 28.
Autoimmune disease is a critical health concern, whose etiology remains enigmatic. We hypothesized that immune responses to somatically mutated self proteins could have a role in the development of autoimmune disease. IFN-γ secretion by T cells stimulated with mitochondrial peptides encoded by published mitochondrial DNA was monitored to test the hypothesis. Human peripheral blood mononuclear cells (PBMCs) of healthy controls and autoimmune patients were assessed for their responses to the self peptides and mutated-self peptides differing from self by one amino acid. None of the self peptides but some of the mutated-self peptides elicited an immune response in healthy controls. In some autoimmune patients, PBMCs responded not only to some of the mutated-self peptides, but also to some of the self peptides, suggesting that there is a breach of self-tolerance in these patients. Although PBMCs from healthy controls failed to respond to self peptides when stimulated with self, the mutated-self peptide could elicit a response to the self peptide upon re-stimulation in vitro, suggesting that priming with mutated-self peptides elicits a cross-reactive response with self. The data raise the possibility that DNA somatic mutations are one of the events that trigger and/or sustain T cell responses in autoimmune diseases.
自身免疫性疾病是一个严重的健康问题，其病因仍然不明。我们推测，对体细胞突变的自身蛋白的免疫反应可能在自身免疫性疾病的发展中起作用。通过监测用已发表的线粒体DNA编码的线粒体肽刺激的T细胞分泌的IFN-γ来检验这一假设。评估健康对照者和自身免疫性疾病患者的人外周血单个核细胞（PBMC）对自身肽和与自身相差一个氨基酸的突变自身肽的反应。在健康对照者中，没有一种自身肽能引发免疫反应，但一些突变自身肽能引发免疫反应。在一些自身免疫性疾病患者中，PBMC不仅对一些突变自身肽有反应，而且对一些自身肽也有反应，这表明这些患者存在自身耐受性的破坏。尽管来自健康对照者的PBMC在用自身刺激时对自身肽无反应，但在体外再次刺激时，突变自身肽能引发对自身肽的反应，这表明用突变自身肽进行预刺激会引发与自身的交叉反应。这些数据增加了DNA体细胞突变是触发和/或维持自身免疫性疾病中T细胞反应的事件之一的可能性。
