Thomas F T, Carver F M, Foil M B, Pryor W H, Larkin E W, Hall W R, Haisch C E, Thomas J M
Ann Surg. 1983 Sep;198(3):370-8. doi: 10.1097/00000658-198309000-00013.
Transplantation between non-identical humans has been limited by the requirement for chronic immunosuppression (CI). This study demonstrates in a nonhuman primate model that long-term acceptance of incompatible kidney allografts can be achieved without the use of CI. Following incompatible kidney transplantation, rhesus monkey recipients were given a 5-day course of clinical rabbit antithymocyte globulin (RATG). On day 12, unfractionated donor bone marrow (BM) was infused intravenously. Recipients were monitored for T-cell levels and T-cell subset levels with monoclonal antibodies and for responses in one way MLR. Graft survival in untreated control animals was 9.2 +/- 2.8 days. In six animals given RATG only, all died of rejection at a mean 35.8 +/- 5.7 days. Of five animals given RATG and donor BM (mean 2.5 RhLA mismatches, mean MLC 12.7), four are alive at 150 days, 248 days, 342 days, and 401 days (median 248 days). The ATG-BM infused group showed a prolonged imbalance of their OKT4/OKT8 cell ratio and cellular suppression of MLR responsiveness. The long-term survival obtained in these outbred primates is apparently due to a synergistic immunoregulatory effect induced by the RATG and donor BM. The model described is apparently the first report of long-term survival of outbred higher primates without CI and may represent a technique for producing tolerance without CI in the human.
非相同人类之间的移植一直受到慢性免疫抑制（CI）需求的限制。本研究在非人灵长类动物模型中表明，不使用CI也可实现对不相容肾移植的长期接受。在进行不相容肾移植后，给恒河猴受体给予为期5天的临床兔抗胸腺细胞球蛋白（RATG）疗程。在第12天，将未分级的供体骨髓（BM）静脉输注。用单克隆抗体监测受体的T细胞水平和T细胞亚群水平以及单向混合淋巴细胞反应（MLR）中的反应。未治疗的对照动物的移植物存活时间为9.2±2.8天。在仅给予RATG的6只动物中，所有动物均在平均35.8±5.7天死于排斥反应。在给予RATG和供体BM的5只动物中（平均2.5个RhLA错配，平均MLC为12.7），4只动物在150天、248天、342天和401天存活（中位数248天）。输注ATG-BM的组显示其OKT4/OKT8细胞比值长期失衡以及MLR反应性的细胞抑制。在这些远交灵长类动物中获得的长期存活显然是由于RATG和供体BM诱导的协同免疫调节作用。所描述的模型显然是关于远交高等灵长类动物在无CI情况下长期存活的首次报道，并且可能代表一种在人类中产生无CI耐受性的技术。
