Therapeutic effect of CD28 superagonist on renal disease via expansion of regulatory T cells

CD28 超级激动剂通过扩增调节性 T 细胞对肾脏疾病的治疗作用

• 批准号: 21591030
• 负责人: TAKABATAKE Yoshitsugu
• 金额: $ 2.91万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591030/
• 关键词: CD28; スーパーアゴニスト; 制御性T細胞; FoxP3; 抗GBM抗体腎炎; 半月体形成性糸球体腎炎; CD163; 半月体形成性腎炎; Thy-1腎炎

We hypothesized that a superagonistic monoclonal antibody for CD28, JJ316, which has been known to preferentially expand Treg cells in vivo, could prevent nephrotoxic serum(NTS)-induced nephritis in Wistar-Kyoto rats. Administration of JJ316 attenuated crescent formation, proteinuria, and glomerular accumulation of macrophages and Treg cells. Among glomerular macrophages, the CD163+ subset was significantly increased after treatment, suggesting that Treg cells may modulate the phenotype of macrophages leading to resolution of GN. Adoptive transfer experiment recapitulated the beneficial effects of in vivo administration of JJ316. Furthermore a single injection of JJ316 administered 3 days after disease induction completely protected nephritic rats from death for 2 months. In conclusion, we have demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic GN, probably due to an expansion of Treg cells.

我们假设CD28，JJ316的一种超振能单克隆抗体，该抗体已众所周知，该抗体在体内优先扩展了Treg细胞，可以预防Wistar-kyoto大鼠中肾毒性血清（NTS）诱导的肾炎。 JJ316的施用减弱了新成年的形成，蛋白尿和巨噬细胞和Treg细胞的肾小球积累。在肾小球巨噬细胞中，治疗后CD163+子集显着增加，这表明Treg细胞可能调节巨噬细胞的表型，从而导致GN解决。收养转移实验概括了JJ316体内给药的有益作用。此外，疾病诱导后3天给药的单一注射JJ316完全保护了肾智力大鼠2个月。总之，我们已经证明，用JJ316的治疗对实验性新月GN具有巨大的治疗作用，这可能是由于Treg细胞的扩展。

项目成果

CD28スーパーアゴニストのラット半月体形成性腎炎に対する治療効果の検討

CD28超激动剂对大鼠新月体肾炎的治疗作用考察

• 发表时间: 2009
• 作者: 高畠義嗣

CD28スーパーアゴニスト

CD28超级激动剂

• 发表时间: 2011
• 期刊: 医学のあゆみ
• 作者: Hiraishi K;Hirose T;Yamamoto H;Shoji I;Shibasaki A;Kato I;Kaneko K;Satoh F;Totsune K;Takahashi K.;高畠義嗣
• 通讯作者: 高畠義嗣

A superagonistic monoclonal antibody for CD28 ameliorates crescentic glomerulonephritis in wistar-kyoto rats

CD28 超激动单克隆抗体可改善 Wistar-Kyoto 大鼠新月体肾小球肾炎

• DOI: 10.2119/molmed.2010.00229
• 发表时间: 2011
• 期刊: Mol Med
• 影响因子: 5.7
• 作者: Takabatake Y

CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats

• DOI: 10.1007/s10157-010-0370-4
• 发表时间: 2011-02-01
• 期刊: CLINICAL AND EXPERIMENTAL NEPHROLOGY
• 影响因子: 2.3
• 作者: Miyasato, Kenro;Takabatake, Yoshitsugu;Isaka, Yoshitaka
• 通讯作者: Isaka, Yoshitaka

ループス腎炎モデルマウスに対するCD28スーパーアゴニストの治療効果の検証

CD28超激动剂对狼疮性肾炎模型小鼠的治疗作用验证

• 发表时间: 2010
• 作者: 高畠義嗣;木村友則;宮里研郎;高橋篤史;植畑拓也;貝森淳哉;川田典孝;今井圓裕;HunigThomas;李小康;楽木宏実;猪阪善隆
• 通讯作者: 猪阪善隆