Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment
Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment
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DOI：
10.1097/00007890-199811270-00021
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发表时间：
1998-11-27
期刊：
影响因子：
6.2
通讯作者：
Strom, TB
中科院分区：
文献类型：
--
作者：
Li, YS;Zheng, XX;Strom, TB
背景抗CD 40配体和CTLA-4 Ig（共刺激阻断剂）联合治疗同种异体移植物受体是一种有前途的治疗方法，尽管不能持续耐受治疗。这将是可取的，使用一个有效的常规免疫抑制方案，在低剂量或短期疗程作为一个辅助;然而，环孢菌素治疗大大减弱的能力，共刺激阻断产生长期的植入。在小鼠BALB/c到C3 H/He异位心脏移植模型中，比较了短疗程的环孢素或雷帕霉素作为共刺激阻断剂的效果。尽管环孢霉素治疗阻断了共刺激阻断剂产生永久植入的能力，但雷帕霉素和共刺激阻断剂联合治疗可产生永久植入。提出了环孢素和雷帕霉素对共刺激阻断结果的不同影响的理论基础。联合应用共刺激阻断剂和雷帕霉素可能为临床应用共刺激阻断剂提供一种方法。
Background. Combined treatment of allograft recipients with anti-CD40 ligand and CTLA-4Ig (costimulation blockade) is a powerful promising albeit not consistently tolerizing therapy. It would be desirable to use an effective conventional immunosuppressive regimen in low doses or for a short course as an adjunct; however, cyclosporine treatment drastically blunts the ability of costimulation blockade to produce longterm engraftment.Methods. Short courses of cyclosporine or rapamycin were compared as adjuncts to costimulation blockade in the murine BALB/c to C3H/He heterotopic cardiac allograft model.Results. Although cyclosporine therapy blocked the capacity of costimulation blockade to produce permanent engraftment, combined rapamycin and costimulation blockade treatment produced permanent engraftment.Conclusion. A theoretical basis for the differing effects of cyclosporine and rapamycin upon the outcome of costimulation blockade is forwarded. Combined use of costimulation blockade and rapamycin may provide a means to bring costimulation blockade into the clinic.