Interleukin 2 receptor-targeted therapy--rationale and applications in organ transplantation.
Interleukin 2 receptor-targeted therapy--rationale and applications in organ transplantation.
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DOI：
10.1097/00007890-198812000-00001
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发表时间：
1988-12
期刊：
影响因子：
6.2
通讯作者：
J. KUPIEC-WEGLINSKI;Tibor Diamantstein;N. Tilney
中科院分区：
文献类型：
--
作者：
J. KUPIEC-WEGLINSKI;Tibor Diamantstein;N. Tilney
尽管免疫药理学在用于临床器官移植方面取得了重大进展，但移植物排斥反应和药物诱导的副作用仍然是目前可用的免疫抑制方法的主要问题。杂交瘤技术的最新进展已经用单抗产生了相对有效和可重复性的生物免疫抑制；事实上，OKT3和抗T12单抗在治疗排斥反应中作为化学抑制的辅助手段已经取得了相当大的成功。然而，在T淋巴细胞上使用这种对分化抗原具有广泛反应的抗体并不能解决全身免疫抑制引起的副作用问题。理想的治疗药物应该只针对参与异体组织排斥反应的淋巴细胞，而不影响生理宿主免疫监视和正常防御机制。从理论上讲，这个目标可以通过“抗原性自杀”来实现，或者通过使用适当的抗独特型抗体或针对T细胞受体的抗原结合部位的单抗来实现。然而，由于移植抗原的高度多态和编码T细胞抗原受体的大量基因谱系，这种形式的特异性免疫抑制的成功是非常不可能的，至少目前是这样。
Despite major advances in immunopharmacology for use in clinical organ transplantation, graft rejection and drug-induced side effects remain the major problems with currently available immunosuppressive modalities. Recent advances in hybridoma technology have produced relatively effective and reproducible biological immunosuppression with monoclonal antibodies; indeed, OKT3 and anti-T12 mAbs have been employed with considerable success as adjuncts to chemical suppression in treating rejection. Nonetheless, the use of such antibodies broadly reactive to differentiation antigens on T lymphocytes does not solve the problems of side effects caused by general immunosuppression. An ideal therapeutic agent should target only lymphocytes that participate in rejection of foreign tissue without affecting physiological host immune surveillance and normal defense mechanisms. Theoretically, this goal could be achieved by "antigenic suicide," or by using the appropriate antiidiotypic antibodies or mAbs against the antigen combining site of T cell receptors. However, because of the intense polymorphism of transplantation antigens and the vast genetic repertoire encoding for the T cell antigen receptor, success of such forms of specific immunosuppression, at least at this time, is highly improbable.