Han Gencheng, Shao Hui, Peng Yong, Zhang Ping, Ke Yan, Kaplan Henry J, Sun Deming
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
J Neuroimmunol. 2007 Feb;183(1-2):81-8. doi: 10.1016/j.jneuroim.2006.11.021. Epub 2006 Dec 28.
To determine whether decreased regulatory T cell activity contributes to the pathogenesis of recurrent experimental autoimmune uveitis (EAU), we compared the immunoregulatory activity of CD8+CD45RClow T cells isolated from rats that had recovered from acute EAU with those from rats with the progressive, recurrent disease. Our results showed that CD8+CD45RClow T cells isolated from the recovered rats showed suppressive activity in vitro, whereas those from rats with progressive, recurrent EAU do not. Depletion of CD8+CD45RClow T cells from T cells used for adoptive transfer of EAU increased the pathogenic activity of the T cells. Co-transfer of CD8+CD45RClow T cells with uveitogenic T cells prevented the relapse of disease in the recipient rats. The suppressive CD8+CD45RClow T cells expressed increased levels of Foxp3 after stimulation in vitro with the autoantigen, and inhibited the production of IFN-gamma by autoreactive T cells. Our data indicate that the decreased suppressive activity of CD8+CD45RClow T cells is correlated with disease development in this autoimmune disease. Further studies on the biology of this T cell population should provide much needed insights into disease pathogenesis.
为了确定调节性T细胞活性降低是否促成复发性实验性自身免疫性葡萄膜炎（EAU）的发病机制，我们比较了从急性EAU恢复的大鼠与患有进行性复发性疾病的大鼠中分离出的CD8 + CD45RClow T细胞的免疫调节活性。我们的结果显示，从恢复的大鼠中分离出的CD8 + CD45RClow T细胞在体外表现出抑制活性，而从患有进行性复发性EAU的大鼠中分离出的细胞则没有。从用于EAU过继转移的T细胞中去除CD8 + CD45RClow T细胞会增加T细胞的致病活性。将CD8 + CD45RClow T细胞与致葡萄膜炎T细胞共同转移可防止受体大鼠疾病复发。体外经自身抗原刺激后，具有抑制作用的CD8 + CD45RClow T细胞表达的Foxp3水平升高，并抑制自身反应性T细胞产生IFN-γ。我们的数据表明，CD8 + CD45RClow T细胞抑制活性降低与这种自身免疫性疾病的疾病发展相关。对该T细胞群体生物学的进一步研究应能为疾病发病机制提供急需的见解。
