The effects of Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody in DSS-induced mice colitis

被引:20
|
作者
Chen, Jiajie [1 ]
Xie, Lin [3 ]
Toyama, Sayaka
Huenig, Thomas [4 ]
Takahara, Shiro [3 ]
Li, Xiao-Kang [2 ]
Zhong, Liang [1 ]
机构
[1] Fudan Univ, Huashan Hosp, Dept Gastroenterol, Shanghai 200040, Peoples R China
[2] Natl Res Inst Child Hlth & Dev, Div Radiat Safety & Immune Tolerance, Setagaya Ku, Tokyo 1578535, Japan
[3] Osaka Univ, Grad Sch Med, Dept Adv Technol Transplantat, Osaka, Japan
[4] Univ Wuurzburg, Inst Virol & Immunbiol, Wuurzburg, Germany
关键词
Antibody; Colitis; Foxp3; Inflammatory bowel disease; Regulatory T cell; INFLAMMATORY-BOWEL-DISEASE; CD28-SPECIFIC MONOCLONAL-ANTIBODIES; VERSUS-HOST DISEASES; IMMUNE-RESPONSES; MURINE COLITIS; CUTTING EDGE; NTREG CELLS; IL-2; INTERLEUKIN-2; HOMEOSTASIS;
D O I
10.1016/j.intimp.2010.11.034
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:610 / 617
页数:8
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