The kinetics of tolerance induction by nondepleting anti-CD4 monoclonal antibody (RIB 5/2) plus intravenous donor alloantigen administration.
The kinetics of tolerance induction by nondepleting anti-CD4 monoclonal antibody (RIB 5/2) plus intravenous donor alloantigen administration.
复制标题
非消耗性抗 CD4 单克隆抗体 (RIB 5/2) 加静脉内供体同种抗原给药诱导耐受的动力学。
DOI：
10.1097/00007890-200001270-00015
复制
发表时间：
2000
期刊：
影响因子：
6.2
通讯作者：
Flye,MW
中科院分区：
文献类型：
--
作者：
Motoyama,K;Arima,T;Yu,S;Lehmann,M;Flye,MW
背景：CD4+T细胞在同种异体移植排斥反应中起着重要作用。抗大鼠CD4的单抗RIB 5/2已被证明在不消除受体T细胞的情况下调节CD4糖蛋白。我们成功地诱导了大鼠同种异体心脏移植的耐受性，方法是受体预先给予单剂量RIB5/2加供者脾细胞静脉注射。在这项研究中，我们探索了这种有效的方案是否可以诱导对更具抵抗力的同种异体肾和皮肤移植的耐受。此外，我们还研究了单次注射肋骨5/2+静脉注射同种异体抗原20 mg/kg+供体抗原(25×106脾细胞)预处理0、21或40天后接受MHC不匹配的Lewis(Rt1 L)与水牛(Rt1b)大鼠心脏、肾脏或皮肤移植的疗效。另一组接受肋骨5/2加静脉注射同种异体胸腺抗原的水牛受体在40天后接受肾移植。试图防止耐受性使用白介素2或事先致敏。结果：RIB5/2联合静脉注射同种异体抗原诱导心脏和肾移植耐受，但不能延长移植皮片的存活时间。相反，在预处理后延迟40天的同种异体肾移植发生了急性排斥反应，而胸腺切除并不影响存活率。长期移植受者的MLC、CTL、PTH和PCTL前体频率对供者有特异性抑制，但对第三方同种异体抗原没有影响。结论：单剂非耗竭的抗CD4单抗RIB 5/2加静脉注射同种异体抗原可有效诱导心脏和肾脏移植物耐受，但不能诱导皮肤耐受。肋骨5/2诱导的供者对延迟的肾或心脏移植物的无反应性是时间依赖的，但如果存在特定的同种异体抗原，则可以延长。抑制细胞介导的同种异体免疫反应与同种异体移植的接受性有关。
Background.CD4+ T cells play an essential role in allograft rejection. The monoclonal anti-rat CD4 antibody, RIB 5/2, has been shown to modulate the CD4 glycoprotein without eliminating the recipient T cells. We have successfully induced tolerance to rat heart allografts by recipient pretreatment with a single dose of RIB 5/2 plus intravenous administration of donor splenocytes. In this study, we explored whether this potent regimen could induce tolerance to the more resistant kidney and skin allografts. Furthermore, we examined the kinetics and requirements for tolerance to be met by a single dose of RIB 5/2 plus iv alloantigen.Methods.The efficacy of a single ip dose of 20 mg/kg RIB 5/2 plus iv donor antigen (25× 10 6 splenocyte) pretreatment 0, 21, or 40 days before receipt of an MHC-mismatched Lewis (RT1 l) to Buffalo (RT1 b) rat cardiac, renal, or skin allograft was studied. Another group of Buffalo recipients treated with RIB 5/2 plus an iv alloantigen±thymectomy received kidney transplants after 40 days. Attempts to prevent tolerance used interleukin-2 or prior sensitization. Mixed lymphocyte cultures, cytotoxic assays, and precursor frequencies of helper and cytotoxic cells, by limiting dilution analysis, serially measured in vitro cell-mediated immunity.Results.RIB 5/2 administration combined with iv alloantigen 21 days before induced tolerance to heart and kidney allografts but did not prolong skin graft survival. In contrast, kidney allografts delayed for 40 days after pretreatment were acutely rejected and survival was not affected by the thymectomy. MLC, CTL, and pTH, and pCTL precursor frequencies from recipients of long-term grafts were specifically suppressed to donor, but not third party, alloantigen.Conclusion.A single dose of the nondepleting anti-CD4 monoclonal antibody, RIB 5/2, plus iv alloantigen is a potent inducer of tolerance to heart and kidney, but not skin, allografts. The RIB 5/2-induced donor unresponsiveness to a delayed kidney or cardiac allograft is time dependent but can be prolonged if specific alloantigen is present. Suppression of cell-mediated allo-immune responsiveness correlates with allograft acceptance.