Hiromatsu K, Aoki Y, Makino M, Matsumoto Y, Mizuochi T, Gotoh Y, Nomoto K, Ogasawara J, Nagata S, Yoshikai Y
Laboratory of Germfree Life, Research Institute for Disease, Nagoya University School of Medicine, Japan.
Eur J Immunol. 1994 Oct;24(10):2446-51. doi: 10.1002/eji.1830241028.
The Fas antigen (Fas), which is a cell surface protein belonging to the tumor necrosis factor receptor family, mediates apoptosis. To assess the contribution of Fas to the pathogenesis of retrovirus-induced immunodeficiency, we examined the kinetics of Fas expression on the lymphocytes during the course of murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine leukemia virus. The Fas-positive cells were increased in proportion both in alpha beta T cells and B cells with the progression of MAIDS. The appearance of Fas-positive cells in alpha beta T cells preceded those in B cells during the course of MAIDS. Among alpha beta T cells, about half of the Thy1.2+ alpha beta T cells were positive for Fas, while almost all of Thy1.2- CD4+ alpha beta T cells were of the Fas-positive phenotype. The Fas-positive cells in MAIDS mice, especially unique Thy1.2-CD4+ alpha beta T cells, were easily rendered apoptotic by stimulation via Fas, indicating that Fas expressed on the lymphocytes is functional. Furthermore, concomitant infection with Mycobacterium avium in MAIDS mice caused a marked increase in Fas-positive cells accompanied by a severely impaired T cell reactivity to polyclonal stimuli. Taken together, these results suggest that possible participation of the Fas system in the pathogenesis of retrovirus-induced immunodeficiency.
Fas抗原(Fas)是一种属于肿瘤坏死因子受体家族的细胞表面蛋白,可介导细胞凋亡。为了评估Fas在逆转录病毒诱导的免疫缺陷发病机制中的作用,我们检测了由缺陷型LP - BM5小鼠白血病病毒诱导的小鼠获得性免疫缺陷综合征(MAIDS)病程中淋巴细胞上Fas表达的动力学变化。随着MAIDS的进展,αβT细胞和B细胞中Fas阳性细胞的比例均增加。在MAIDS病程中,αβT细胞中Fas阳性细胞的出现早于B细胞。在αβT细胞中,约一半的Thy1.2 +αβT细胞Fas呈阳性,而几乎所有Thy1.2 - CD4 +αβT细胞均为Fas阳性表型。MAIDS小鼠中的Fas阳性细胞,尤其是独特的Thy1.2 - CD4 +αβT细胞,通过Fas刺激很容易发生凋亡,这表明淋巴细胞上表达的Fas具有功能。此外,MAIDS小鼠同时感染鸟分枝杆菌会导致Fas阳性细胞显著增加,同时T细胞对多克隆刺激的反应性严重受损。综上所述,这些结果提示Fas系统可能参与了逆转录病毒诱导的免疫缺陷的发病机制。