The effects of Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody in DSS-induced mice colitis
The effects of Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody in DSS-induced mice colitis
复制标题
DOI：
10.1016/j.intimp.2010.11.034
复制
发表时间：
2011-05-01
影响因子：
5.6
通讯作者：
Zhong, Liang
中科院分区：
文献类型：
--
作者：
Chen, Jiajie;Xie, Lin;Zhong, Liang
调节性T（Treg）细胞在炎症性肠病（IBD）的发病机制中起重要作用。在本研究中，我们发现一种超激动性CD 28特异性单克隆抗体（supCD 28 mAb. D 665）可以优先刺激CD 4 + Foxp 3 + Treg细胞的扩增。Foxp 3（EGFP）小鼠经口给予3.5%DSS 5天，治疗组腹腔注射supCD 28 mAb 1 mg/只。所有小鼠在第8天处死，临床和组织学参数均显示与对照组相比，治疗组的结肠炎严重程度显著降低。治疗组小鼠脾脏和肠系膜淋巴结Foxp 3 +Treg细胞表达CD 103、CD 152和CD 62 L的比例均高于对照组。qRT-PCR分析显示，治疗组IL-10、TCF-β等抗炎细胞因子的表达明显增加。综上所述，我们的数据表明supCD 28 mAb在体内靶向CD 4 + Foxp 3 +Treg细胞扩增，维持并增强其调节功能，通过分泌大量IL-10减轻葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎中结肠的损伤。它代表了多克隆活化的Treg细胞作为治疗IBD的细胞疗法的治疗用途的重大进展。(C)2010爱思唯尔有限公司版权所有。
Regulatory T (Treg) cells play an important role in the pathogenesis of inflammatory bowel disease (IBD). In the present study, we found that a superagonistic CD28-specific monoclonal antibody (supCD28mAb. D665) could preferentially stimulate expansion of CD4+Foxp3+ Treg cells. Foxp3(EGFP) mice were orally administrated with 3.5% DSS for 5 days, and intraperitoneally injected supCD28mAb 1 mg/mice in treated group. All of the mice were sacrificed on day 8, and both clinical and histological parameters showed that the severity of colitis was significantly reduced in treated group compared to controls. In treated group, the proportion of CD103, CD152 and CD62L expression on Foxp3+Treg cells in the spleen and mesenteric lymph node were higher than controls. Furthermore, qRT-PCR analysis showed that expression of anti-inflammatory cytokines such as IL-10, TCF-beta was significantly increased in treated group. Taken together, our data demonstrated that supCD28mAb targets CD4+Foxp3+Treg cells expansion in vivo, maintains and enhances their regulatory functions, to reduce the damage of colon in dextran sulfate sodium (DSS)-induced mouse colitis by secreting a large amount of IL-10. It represents a major advance towards the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of IBD. (C) 2010 Elsevier B.V. All rights reserved.