CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease
CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease
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DOI：
10.1681/asn.2005080842
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发表时间：
2006-10-01
影响因子：
13.6
通讯作者：
Harris, David C. H.
中科院分区：
文献类型：
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作者：
Mahajan, Deepika;Wang, Yiping;Harris, David C. H.
CD4(+)CD25(+)调节性T细胞(Treg)疾病调节机制的研究重点是它们与效应T细胞的相互作用。然而，调节可能涉及非同源细胞的可能性尚未得到详细探讨。本研究在体外研究了 CD4(+)CD25(+) Treg 对巨噬细胞促炎特性和表型的影响，发现它们通过抑制巨噬细胞的活化来调节巨噬细胞，导致促炎细胞因子的产生减少和效应表型下调。为了测试这种效应的体内显着性，在诱导阿霉素肾病（一种慢性肾病的非同源模型）后，将表达高水平 Foxp3 的 CD4(+)CD25(+) T 细胞重建到 SCID 小鼠中。 CD4(+)CD25(+) T细胞显着减轻肾小球和间质损伤。此外，与单独阿霉素组相比，用Treg重建的SCID小鼠的肾小球和间质中的巨噬细胞数量显着下降。使用中和抗体阻断 TGF-β 会显着削弱 Treg 的保护作用。这些发现描述了 TGF-β 依赖性 Treg-巨噬细胞抑制相互作用，可以解释 Treg 的同源独立保护。
Studies of mechanisms of disease regulation by CD4(+)CD25(+) regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4(+)CD25(+) Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4(+)CD25(+) T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4(+)CD25(+) T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.