Dono K, Maki T, Wood M L, Monaco A P
Department of Surgery, Deaconess Hospital, Boston, Massachusetts 02215, USA.
Transplantation. 1995 Dec 15;60(11):1268-73.
The effect of donor-recipient strain combination and supplemental rapamycin (Rapa) on tolerance induction by intrathymic (IT) injection of donor splenocytes was examined in a mouse skin allograft model. In an MHC class I-mismatched C3H/He skin to (C57BL/6 x A)F1 (B6AF1) mouse combination, IT injection of 50 x 10(6) donor splenocytes with transient immunosuppression by rabbit anti-mouse lymphocyte serum (ALS) induced significant prolongation of skin allograft survival with a median survival time (MST) of 115 days versus an MST of 24.5 days in controls given ALS alone. With an additional short course of supplemental Rapa treatment at a dose of 1.5 mg/kg i.p. every other day from day 0 to 12, all C3H/He skin allografts survived indefinitely (> 350 days) in ALS-treated, donor splenocyte intrathymically injected B6AF1 recipient mice. Tolerance was antigen-specific, since the second donor-type skin allografts were accepted while third-party skin allografts were acutely rejected in these mice bearing long-term C3H/He skin allografts. In MHC class I- and II-disparate (DBA/2 to B6AF1) and fully MHC-incompatible (AKR to B6) strain combinations, IT injection of donor splenocytes and ALS treatment failed to prolong skin allograft survival over ALS controls. When supplemental Rapa was used, long-term skin allograft acceptance was observed with an MST of 127 days for the DBA/2 to B6AF1 combination and 70 days for the AKR to B6 combination. In contrast, supplemental treatment with cyclosporine was not effective in these combinations, which suggests that supplemental Rapa may have a unique effect in augmenting IT tolerance induction. Thymectomy within 7 days after IT injection significantly shortened the allograft survival, which suggests that interaction of the host thymus and the injected donor splenocytes, which takes place early after IT injection, plays an important role in the induction of allograft tolerance in this model.
在小鼠皮肤同种异体移植模型中，研究了供体 - 受体品系组合及补充雷帕霉素（Rapa）对胸腺内（IT）注射供体脾细胞诱导免疫耐受的影响。在MHC I类不匹配的C3H/He皮肤至（C57BL/6×A）F1（B6AF1）小鼠组合中，IT注射50×10⁶个供体脾细胞并联合兔抗小鼠淋巴细胞血清（ALS）进行短暂免疫抑制，可显著延长皮肤同种异体移植的存活时间，中位存活时间（MST）为115天，而单独给予ALS的对照组MST为24.5天。从第0天至12天每隔一天腹腔注射剂量为1.5mg/kg的Rapa进行额外的短期补充治疗后，在接受ALS治疗且经胸腺内注射供体脾细胞的B6AF1受体小鼠中，所有C3H/He皮肤同种异体移植均无限期存活（>350天）。这种耐受具有抗原特异性，因为在这些长期接受C3H/He皮肤同种异体移植的小鼠中，第二次供体类型的皮肤同种异体移植被接受，而第三方皮肤同种异体移植则被急性排斥。在MHC I类和II类均不相容（DBA/2至B6AF1）以及完全MHC不匹配（AKR至B6）的品系组合中，IT注射供体脾细胞和ALS治疗未能使皮肤同种异体移植的存活时间超过ALS对照组。使用补充Rapa后，观察到长期的皮肤同种异体移植接受情况，DBA/2至B6AF1组合的MST为127天，AKR至B6组合的MST为70天。相比之下，环孢素的补充治疗在这些组合中无效，这表明补充Rapa可能在增强IT诱导的耐受方面具有独特作用。IT注射后7天内进行胸腺切除显著缩短了同种异体移植的存活时间，这表明宿主胸腺与注射的供体脾细胞之间的相互作用在IT注射后早期发生，在该模型中同种异体移植耐受的诱导中起重要作用。
