Ludewig B, McCoy K, Pericin M, Ochsenbein A F, Dumrese T, Odermatt B, Toes R E, Melief C J, Hengartner H, Zinkernagel R M
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Zürich, Switzerland.
J Immunol. 2001 Mar 15;166(6):3678-87. doi: 10.4049/jimmunol.166.6.3678.
This study evaluated to what extent presentation of exogenously acquired self-Ags via MHC class I molecules on DC might contribute to the activation of self-reactive CTL and subsequent development of autoimmune disease. We show here by using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein model of autoimmune diabetes that the activation of self-reactive CTL by DC after uptake of exogenous Ag is very limited, first by the short half-life of MHC class I-associated peptides on DC in vitro and in vivo, and second by the rather inefficient MHC class I presentation of cell-associated self-Ags by DC. These two mechanisms are probably crucial in establishing high thresholds for the induction of self-reactive CTL that prevent autoimmune sequelae after release of sequestered and previously immunologically ignored tissue Ags.
本研究评估了树突状细胞（DC）通过MHC I类分子呈递外源性获得的自身抗原在多大程度上可能有助于自身反应性细胞毒性T淋巴细胞（CTL）的激活以及自身免疫性疾病的后续发展。我们在此通过使用自身免疫性糖尿病的大鼠胰岛素启动子淋巴细胞性脉络丛脑膜炎病毒糖蛋白模型表明，DC摄取外源性抗原后对自身反应性CTL的激活非常有限，首先是因为体外和体内DC上MHC I类相关肽的半衰期较短，其次是因为DC对细胞相关自身抗原的MHC I类呈递效率相当低。这两种机制可能对于建立诱导自身反应性CTL的高阈值至关重要，该阈值可防止在隔离的和先前免疫忽视的组织抗原释放后出现自身免疫后遗症。
