Yamagami S, Tsuru T, Ohkawa T, Endo H, Isobe M
Department of Ophthalmology, Jichi Medical School, Tochigi, Japan.
Transplantation. 1999 Feb 27;67(4):600-4. doi: 10.1097/00007890-199902270-00019.
Anti-alphabeta T cell receptor monoclonal antibody (R73) has been reported to be a potent immunosuppressant. The suppressive effects of this antibody on allograft rejection after corneal transplantation are unknown.
Orthotopic rat penetrating keratoplasty was performed using Lewis rats as recipients and Brown Norway and Fisher rats as donors. The treated groups received R73 intraperitoneally until day 12 after the transplantation. In grafted rats with or without R73 treatment, cytokine expression of the aqueous humor, corneal-infiltrating cells, draining lymph nodes, and splenocytes was determined. Delayed-type hypersensitivity (DTH) responses were compared.
All allografts in the untreated controls of Fisher-to-Lewis or BN-to-Lewis rat combinations were rejected within 14 days. In contrast, indefinite survival rates of the postoperative R73-treated group increased to 86% in the Fisher-to-Lewis and 23% in the Brown Norway-to-Lewis combinations, respectively. Interferon-y, interleukin (IL)-2 (T helper [Th]1), and IL-10 (Th2), but not IL-4 (Th2), expression of the eye and DTH responses in the control group were suppressed in the R73-treated group. Both IL-2 and IL-10 expression after mixed lymphocyte culture in the R73-treated group were significantly lower than those of the naive and untreated control group.
alphabeta T cell receptor-targeted therapy prevents allograft rejection in rat corneal transplantation as evidenced by suppression of DTH responses. The cytokine profile after R73 treatment was characterized by low interferon-gamma, IL-2, and IL-10, and high IL-4 expression.
据报道，抗αβT细胞受体单克隆抗体（R73）是一种有效的免疫抑制剂。该抗体对角膜移植后同种异体移植排斥反应的抑制作用尚不清楚。
以Lewis大鼠为受体，Brown Norway大鼠和Fisher大鼠为供体，进行原位大鼠穿透性角膜移植。治疗组腹腔注射R73，直至移植后第12天。在接受或未接受R73治疗的移植大鼠中，测定房水、角膜浸润细胞、引流淋巴结和脾细胞的细胞因子表达。比较迟发型超敏反应（DTH）。
Fisher大鼠至Lewis大鼠或BN大鼠至Lewis大鼠组合的未治疗对照组中的所有同种异体移植均在14天内被排斥。相比之下，术后R73治疗组的无限期存活率在Fisher大鼠至Lewis大鼠组合中升至86%，在Brown Norway大鼠至Lewis大鼠组合中升至23%。R73治疗组中，对照组眼中的干扰素-γ、白细胞介素（IL）-2（辅助性T细胞[Th]1）和IL-10（Th2）表达以及DTH反应均受到抑制。R73治疗组混合淋巴细胞培养后的IL-2和IL-10表达均显著低于未处理的对照组和未免疫的对照组。
靶向αβT细胞受体的治疗可预防大鼠角膜移植中的同种异体移植排斥反应，DTH反应受到抑制证明了这一点。R73治疗后的细胞因子谱特征为干扰素-γ、IL-2和IL-10水平低，IL-4表达高。
