Lazarovits A I, Shield C F
Division of Nephrology, Ottawa General Hospital, Canada.
Clin Immunol Immunopathol. 1988 Sep;48(3):392-400. doi: 10.1016/0090-1229(88)90033-5.
Allograft rejection is the single largest impediment to successful transplantation. Therapy targeted to lymphocytes has been in practice for many years using polyclonal heteroantisera. These products are generally accepted as being useful for the prevention and treatment of rejection; however, there have been problems with specificity, lot to lot variability, and supply. Therapy with monoclonal antibodies such as OKT3 may circumvent these problems and may allow for refined specificity. OKT3 has been shown to be highly effective at reversing acute renal allograft rejection. The few treatment failures were attributed to anti-mouse antibodies eliminating the OKT3, or to delay of therapy to such a late stage that rejection was irreversible. We present two cases which demonstrate successful reversal of acute rejection in cadaveric renal transplants by OKT3. The reversal was transient, however, in both cases, as both patients experienced recurrence of rejection while still receiving the monoclonal antibody. This occurred despite the absence of CD3-positive cells in the peripheral blood, and the presence of excess OKT3 in the serum. This implies that CD3-negative lymphocytes may under certain circumstances contribute to the rejection phenomenon.
同种异体移植排斥是成功移植的最大单一障碍。针对淋巴细胞的治疗已经使用多克隆异种抗血清进行了多年。这些产品通常被认为对预防和治疗排斥有用；然而，存在特异性、批次间变异性和供应方面的问题。使用单克隆抗体如OKT3进行治疗可能会规避这些问题，并可能实现更精确的特异性。OKT3已被证明在逆转急性肾移植排斥方面非常有效。少数治疗失败归因于抗小鼠抗体清除了OKT3，或治疗延迟到排斥不可逆的晚期。我们报告两例病例，显示OKT3成功逆转了尸体肾移植中的急性排斥。然而，在这两例病例中，排斥的逆转都是短暂的，因为两名患者在仍接受单克隆抗体治疗时都经历了排斥复发。尽管外周血中没有CD3阳性细胞，血清中存在过量的OKT3，但仍发生了这种情况。这意味着在某些情况下，CD3阴性淋巴细胞可能促成排斥现象。
