Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma.
Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma.
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DOI：
10.1186/ar1500
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发表时间：
2005
影响因子：
4.9
通讯作者：
Matthys, Patrick
中科院分区：
文献类型：
--
作者：
Kelchtermans, Hilde;De Klerck, Bert;Mitera, Tania;Van Balen, Maarten;Bullens, Dominique;Billiau, Alfons;Leclercq, Georges;Matthys, Patrick
缺乏 IFN-γ 或 IFN-γ 受体 (IFN-γR) 的小鼠更容易患胶原诱导性关节炎 (CIA)，这是一种依赖于使用完全弗氏佐剂 (CFA) 的实验性自身免疫性疾病。在此，我们报告称，IFN-γR 敲除 (KO) 小鼠的易感性升高与 CD4+CD25+ Treg 细胞的功能损伤有关。在用 II 型胶原 (CII) CFA 辅助免疫后，用消耗抗 CD25 抗体治疗野生型小鼠，显着加速了关节炎的发作，并增加了 CIA 的严重程度。这表明 Treg 细胞在 CIA 效应期中发挥作用。 IFN-γR缺陷不影响中央和外周淋巴组织中CD4+CD25+T细胞的数量。此外，从初始 IFN-γR KO 小鼠中分离的 CD4+CD25+ T 细胞在体外具有抑制 T 细胞增殖的正常潜力。然而，在 CFA 中使用 CII 进行免疫后，IFN-γR 缺陷小鼠中 CD4+CD25+ T 细胞的抑制活性明显受损。此外，Treg 细胞的高度特异性标记物 Foxp3 的 mRNA 表达较低。我们进一步证明，内源性 IFN-γ 的作用（在野生型小鼠中具有更多的抑制活性）涉及 Treg 细胞和辅助细胞。我们的结果表明，CIA 中 Treg 细胞活性的降低受到内源性 IFN-γ 的反向调节。
Mice with a deficiency in IFN-γ or IFN-γ receptor (IFN-γR) are more susceptible to collagen-induced arthritis (CIA), an experimental autoimmune disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility of IFN-γR knock-out (KO) mice is associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II (CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role of Treg cells in the effector phase of CIA. IFN-γR deficiency did not affect the number of CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition, CD4+CD25+ T cells isolated from naive IFN-γR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more impaired in IFN-γR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly specific marker for Treg cells, was lower. We further demonstrated that the effect of endogenous IFN-γ, which accounts for more suppressive activity in wild-type mice, concerns both Treg cells and accessory cells. Our results demonstrate that the decrease in Treg cell activity in CIA is counter-regulated by endogenous IFN-γ.