Knechtle S J, Vargo D, Fechner J, Zhai Y, Wang J, Hanaway M J, Scharff J, Hu H, Knapp L, Watkins D, Neville D M
Department of Surgery, University of Wisconsin, Madison 53792, USA.
Transplantation. 1997 Jan 15;63(1):1-6. doi: 10.1097/00007890-199701150-00002.
Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model.
In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were injected intrathymically into some animals.
All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients.
In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.
在抗T细胞药物诱导受体成熟淋巴细胞数量减少的情况下，移植耐受而非免疫可能更受青睐。一种新型免疫抑制剂FN18-CRM9，已知其能高效特异性杀伤T细胞，在一个移植模型中进行了评估。
为清除受体T细胞，将免疫毒素FN18-CRM9给予 MHC 不匹配的肾移植恒河猴受体。将供体淋巴细胞经胸腺内注射到部分动物体内。
所有经免疫毒素使T细胞耗竭的猴子均有移植肾长期存活，6只长期存活受体中的5只经皮肤移植证实存在耐受。
在这个与临床相关的模型中，单一药物导致的深度但短暂的T细胞耗竭可显著促进耐受。
