Erben Ulrike, Pawlowski Nina N, Doerfel Katja, Loddenkemper Christoph, Hoffmann Jörg C, Siegmund Britta, Kühl Anja A
Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
Institute of Pathology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
Clin Immunol. 2015 Mar;157(1):16-25. doi: 10.1016/j.clim.2015.01.004. Epub 2015 Jan 14.
The cell adhesion molecule CD2 facilitates antigen-independent T-cell activation and CD2 deficiency or blockade reduces intestinal inflammation in murine models. We here aimed to evaluate the therapeutic potential of monoclonal antibodies (mAb) specific for human CD2 in colitis treatment. Transfer colitis induced by naïve CD4(+) T cells expressing human CD2 was treated with anti-human CD2 mAb. The mAb CB.219 protected from severe colitis in a preventive treatment regimen, while therapeutic treatment ameliorated intestinal inflammation. Diminished intestinal tissue damage was paralleled by a profound suppression of lamina propria lymphocytes to produce pro-inflammatory cytokines and tumor necrosis factor α as well as the neutrophil chemoattractant CXC motif ligand 1 and the CC chemokine ligand 3. Furthermore, infiltration with macrophages and T cells was low. Thus, reduced intestinal inflammation in our humanized colitis model by targeting CD2 on T cells with the mAb CB.219 suggests a novel approach for colitis treatment.
细胞黏附分子CD2促进抗原非依赖性T细胞活化，在小鼠模型中，CD2缺陷或阻断可减轻肠道炎症。我们在此旨在评估特异性针对人CD2的单克隆抗体（mAb）在结肠炎治疗中的治疗潜力。用抗人CD2 mAb治疗由表达人CD2的幼稚CD4(+) T细胞诱导的转移型结肠炎。mAb CB.219在预防性治疗方案中可预防严重结肠炎，而治疗性治疗可改善肠道炎症。肠道组织损伤减轻的同时，固有层淋巴细胞产生促炎细胞因子和肿瘤坏死因子α以及中性粒细胞趋化因子CXC基序配体1和CC趋化因子配体3的能力受到显著抑制。此外，巨噬细胞和T细胞的浸润较少。因此，在我们的人源化结肠炎模型中，通过用mAb CB.219靶向T细胞上的CD2来减轻肠道炎症，提示了一种治疗结肠炎的新方法。
