Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China; Division for Radiation Safety and Immune Tolerance, National Research Institute for Child Health and Development, Tokyo, Japan.
Int Immunopharmacol. 2011 May;11(5):610-7. doi: 10.1016/j.intimp.2010.11.034. Epub 2010 Dec 14.
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 5days, and intraperitoneally injected supCD28mAb 1mg/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, TGF-β 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.
调节性 T（Treg）细胞在炎症性肠病（IBD）的发病机制中起着重要作用。在本研究中，我们发现一种超激动型 CD28 特异性单克隆抗体（supCD28mAb，D665）可以优先刺激 CD4+Foxp3+Treg 细胞的扩增。Foxp3（EGFP）小鼠口服 3.5% DSS 5 天，并用 1mg/mouse 的 supCD28mAb 腹腔注射治疗组。所有小鼠均于第 8 天处死，与对照组相比，治疗组的临床和组织学参数均显示结肠炎的严重程度显著降低。在治疗组中，Foxp3+Treg 细胞在脾脏和肠系膜淋巴结上的 CD103、CD152 和 CD62L 表达比例高于对照组。此外，qRT-PCR 分析表明，治疗组抗炎细胞因子如 IL-10、TGF-β 的表达显著增加。综上所述，我们的数据表明，supCD28mAb 可在体内靶向扩增 CD4+Foxp3+Treg 细胞，维持并增强其调节功能，通过分泌大量的 IL-10 减轻葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎对结肠的损伤。这代表着将多克隆激活的 Treg 细胞作为细胞疗法治疗 IBD 的治疗用途取得了重大进展。
