Silva Marcos V, Machado Juliana R, Rocha Laura P, Castellano Lúcio R, Reis Marlene A, Corrêa Rosana R M
Immunology Laboratory, Department of Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
J Transplant. 2012;2012:203780. doi: 10.1155/2012/203780. Epub 2012 Jun 7.
Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.
肾脏是人类最常进行移植的器官之一。免疫抑制剂可预防或逆转大多数急性排斥反应；然而，移植肾仍可能因慢性排斥反应而失功。慢性排斥反应过程中的免疫反应依赖于固有免疫和适应性免疫反应。在适应性免疫反应中，T淋巴细胞在慢性排斥反应中起关键作用。同时，我们旨在概述用于调控同种异体移植物中淋巴细胞激活机制的最新策略，重点介绍B7-CD28超家族的T淋巴细胞共刺激和共抑制分子。深入了解这些分子的结构和功能，既能增进对免疫系统本身的认识，也有助于了解它们作为排斥诱导剂或耐受促进剂的潜在作用。在此背景下，CD28家族所起的核心作用，尤其是CD28与CTLA-4之间的关系，成为旨在提高同种异体移植物存活率和减少自身免疫现象的免疫治疗开发的一个有趣靶点。阿巴西普和贝拉西普近期的研发取得了良好结果，具有潜在临床应用价值，这让人们对移植患者的预后产生了更好的期望。
