Erben U, Pawlowski N N, Heimesaat M M, Loddenkemper C, Doerfel K, Spieckermann S, Siegmund B, Kühl A A
Medical Department (Gastroenterology, Infectious Diseases, Rheumatology), Campus Benjamin Franklin, Chari té - Universitätsmedizin Berlin , Berlin, Germany ; Research Center ImmunoSciences, Charité - Universitätsmedizin Berlin , Berlin, Germany.
Immatics Biotechnologies GmbH , Tübingen, Germany.
Eur J Microbiol Immunol (Bp). 2015 Nov 12;5(4):306-15. doi: 10.1556/1886.2015.00040. eCollection 2015 Dec.
Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control. Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasma (T.) gondii and treated with the human CD2-specific mAb CB.219 in a preventive setting. The intestinal T. gondii loads in CB.219 treated mice did not differ from the control group. Histologically, huCD2tg mice showed moderate ileal inflammation that did not change with CB.219 treatment. In the ileum, CB.219 treatment reduced the protein levels of interferon-γ, transforming growth factor β and interleukin-6, whereas interleukin-18 mRNA was slightly increased. The infiltration of neutrophils, macrophages, and T cells into the ileum was unaffected by CB.219 treatment. However, CB.219 treatment decreased the numbers of forkhead box P3(+) regulatory T cells (Treg) in ileum and liver of huCD2tg mice. This was confirmed in vitro using human peripheral blood mononuclear cells. Taken together, targeting CD2(+) T cells by the human CD2 mAb CB.219 does not prevent beneficial immune reactions necessary for pathogen control. Further experiments will address gut specificity, underlying mechanisms, and general applicability of CB.219 treatment.
用单克隆抗体（mAb）CB.219靶向人类CD2可减轻结肠炎模型中的肠道炎症，该模型中T细胞携带人类CD2。在此，我们探究了这种单克隆抗体对感染控制是否有不良影响。在预防性实验中，对T细胞表达人类CD2的小鼠（huCD2tg）口服感染刚地弓形虫，并用人CD2特异性单克隆抗体CB.219进行治疗。CB.219治疗组小鼠的肠道弓形虫载量与对照组无差异。组织学上，huCD2tg小鼠表现出中度回肠炎症，CB.219治疗后炎症未改变。在回肠中，CB.219治疗降低了干扰素-γ、转化生长因子β和白细胞介素-6的蛋白水平，而白细胞介素-18的mRNA略有增加。CB.219治疗对中性粒细胞、巨噬细胞和T细胞向回肠的浸润没有影响。然而，CB.219治疗降低了huCD2tg小鼠回肠和肝脏中叉头框P3（+）调节性T细胞（Treg）的数量。这在体外用人外周血单核细胞得到了证实。综上所述，人CD2单克隆抗体CB.219靶向CD2（+）T细胞不会阻止病原体控制所需的有益免疫反应。进一步的实验将探讨CB.219治疗的肠道特异性、潜在机制和普遍适用性。
