IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells
IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells
复制标题
DOI：
10.1093/intimm/dxh029
复制
发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Weiner, HL
中科院分区：
文献类型：
--
作者：
Zhang, XM;Koldzic, DN;Weiner, HL
CD25(+)CD4（+）调节性T细胞在体外和体内抑制自身反应性T细胞的激活，抑制器官特异性自身免疫性疾病。CD25(+)CD4(+) T细胞调控实验性自身免疫性脑脊髓炎（EAE）的机制尚不清楚。为了评估CD25(+)CD4(+) T细胞在EAE中的作用，我们用髓磷脂蛋白脂蛋白（PLP）（139-151）免疫SJL小鼠以发生EAE，并用抗CD25单抗治疗。免疫后使用抗cd25抗体治疗可显著提高EAE疾病的严重程度和死亡率。抗cd25单抗小鼠中枢神经系统（CNS）炎症增加。抗CD25抗体处理导致血液、外周淋巴结（LN）和脾脏中CD25(+)CD4(+) T细胞百分比下降，这与体外PLP130-151刺激LN细胞产生ifn - γ增加和IL-10产生减少有关。此外，从幼年SJL小鼠转移CD25(+)CD4（+）调节性T细胞可降低活动性EAE的严重程度。体外抗cd3刺激的幼年SJL小鼠CD25(+)CD4(+) T细胞分泌IL-10和IL-10可溶性受体（sR）部分逆转了CD25(+)CD4(+) T细胞的体外抑制活性。来自il -10缺陷小鼠的CD25(+)CD4(+) T细胞不能抑制活性EAE。这些发现表明CD25(+)CD4(+) T细胞在主动诱导的EAE中抑制病原性自身反应性T细胞，并提示它们可能通过涉及IL-10的机制在控制CNS自身免疫性疾病中发挥重要的自然调节功能。
CD25(+)CD4(+) regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ-specific autoimmune diseases. The mechanism of CD25(+)CD4(+) T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25(+)CD4(+) T cells in EAE, SJL mice were immunized with myelin proteolipid protein (PLP)(139-151) to develop EAE and were treated with anti-CD25 mAb. Treatment with anti-CD25 antibody following immunization resulted in a significant enhancement of EAE disease severity and mortality. There was increased inflammation in the central nervous system (CNS) of anti-CD25 mAb-treated mice. Anti-CD25 antibody treatment caused a decrease in the percentage of CD25(+)CD4(+) T cells in blood, peripheral lymph node (LN) and spleen associated with increased production of IFN-gamma and a decrease in IL-10 production by LN cells stimulated with PLP130-151 in vitro. In addition, transfer of CD25(+)CD4(+) regulatory T cells from naive SJL mice decreased the severity of active EAE. In vitro, anti-CD3-stimulated CD25(+)CD4(+) T cells from naive SJL mice secreted IL-10 and IL-10 soluble receptor (sR) partially reversed the in vitro suppressive activity of CD25(+)CD4(+) T cells. CD25(+)CD4(+) T cells from IL-10-deficient mice were unable to suppress active EAE. These findings demonstrate that CD25(+)CD4(+) T cells suppress pathogenic autoreactive T cells in actively induced EAE and suggest they may play an important natural regulatory function in controlling CNS autoimmune disease through a mechanism that involves IL-10.