Harvard Medical School, Department of Surgery, Transplant Institute at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Boston, MA, USA.
Am J Transplant. 2012 May;12(5):1296-302. doi: 10.1111/j.1600-6143.2012.03973.x. Epub 2012 Mar 5.
Preclinical studies in nonhuman primates (NHP) are particularly useful to evaluate the safety and efficacy of new therapeutic proteins developed for use in clinical transplantation. We hypothesized that a treatment that selectively destroys activated cytopathic donor reactive T cells while sparing resting and immunoregulatory T cells in a mouse model might also produce long-term drug-free engraftment and tolerance without the hazards of lymphopenia in the challenging nonhuman primate islet allograft model. Short-term treatment with a regimen consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig cytolytic fusion proteins (triple therapy) posttransplantation results in prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow progressive loss of islet function in some recipients was not associated with obvious pathologic evidence of rejection.
非人类灵长类动物（NHP）的临床前研究对于评估新开发的用于临床移植的治疗性蛋白质的安全性和疗效特别有用。我们假设，在一种选择性地破坏激活的细胞毒性供体反应性 T 细胞，同时保留静息和免疫调节性 T 细胞的小鼠模型中，这种治疗方法也可能在具有挑战性的非人类灵长类胰岛同种异体移植模型中产生无药物的长期移植物植入和耐受，而不会出现淋巴细胞减少的危险。移植后用雷帕霉素、IL-2.Ig 和突变型拮抗型 IL-15.Ig 细胞溶解融合蛋白（三联疗法）进行短期治疗可导致食蟹猴胰岛同种异体移植物的无药物长期植入。此外，一些受者的胰岛功能逐渐丧失，但没有明显的排斥病理证据。
