Schattner A
Department of Virology, Weizmann Institute of Science, Rehovot, Israel.
Am J Med Sci. 1988 Jun;295(6):532-44. doi: 10.1097/00000441-198806000-00007.
Autoimmunity can be accelerated in several genetically prone murine models and can even be induced in normal mice by treatment with interferon (IFN) or IFN-inducers. Several cases of IFN-induced autoimmune disease in humans also have been observed; however, more striking is the fact that some of the clinical manifestations in autoimmune diseases and many of the immunological aberrations can be mediated or enhanced by IFN. The finding of high levels of circulating IFN in many patients may be highly significant in that respect, and the characterization of the predominant type of IFN as an unusual acid-labile IFN-alpha may indicate an infectious etiologic agent in autoimmunity, since this peculiar IFN was mostly associated with viral infections in vivo or in vitro. The induction of MHC class II antigens on previously HLA-DR or Ia negative cells appears to be caused primarily by IFN-gamma and may have a central role in the pathogenesis of autoimmunity in susceptible individuals. Such aberrant HLA-DR expression on nonlymphoid cells can be detected early in the disease in the target organs of many varied autoimmune conditions and may trigger a cascade of self-directed, uncontrolled immune response in conjunction with other factors.
在几种具有遗传易感性的小鼠模型中，自身免疫可被加速，甚至通过用干扰素（IFN）或IFN诱导剂处理，可在正常小鼠中诱发自身免疫。在人类中也观察到几例IFN诱导的自身免疫性疾病；然而，更引人注目的是，自身免疫性疾病中的一些临床表现以及许多免疫异常可由IFN介导或增强。在这方面，许多患者循环中IFN水平升高这一发现可能具有高度重要性，而将主要类型的IFN鉴定为一种不寻常的酸不稳定IFN-α，可能表明自身免疫中有感染性病因，因为这种特殊的IFN在体内或体外大多与病毒感染相关。先前HLA-DR或Ia阴性细胞上MHC II类抗原的诱导似乎主要由IFN-γ引起，并且可能在易感个体自身免疫的发病机制中起核心作用。在许多不同自身免疫性疾病的靶器官中，疾病早期即可检测到非淋巴细胞上这种异常的HLA-DR表达，并且可能与其他因素一起引发一系列自我导向、不受控制的免疫反应。
