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首页> 外文期刊>Expert opinion on biological therapy >T-cell co-stimulatory blockade in transplantation: Two steps forward one step back!
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T-cell co-stimulatory blockade in transplantation: Two steps forward one step back!

机译：移植中的T细胞共刺激性阻断：前进两步，退后一步！

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Introduction: The concern about nephrotoxicity with calcineurin inhibitors led to the search of novel agents for immunosuppression. Based on the requirement of T-cell co-stimulatory signals to fully activated na?ve T cells, it became clear that blocking these pathways could be an appealing therapeutic target. However, some unexpected findings were noticed in the recent clinical trials of belatacept, including a higher rate of rejection, which warranted further investigation with some interesting concepts emerging from the bench. Areas covered: This article aims to review the literature of the B7:CD28 co-stimulatory blockade in transplantation, including the basic immunology behind its development, clinical application and potential limitations. Expert opinion: Targeting co-stimulatory pathways were found to be much more complex than initially anticipated due to the interplay between not only various co-stimulatory pathways but also various co-inhibitory ones. In addition, co-stimulatory signals have different roles in diverse immune cell types. Therefore, targeting CD28 ligands with cytotoxic T lymphocyte antigen-4 (CTLA4)-Ig may have some deleterious effects, including the inhibition of regulatory T cells, blockade of co-inhibitory signals (CTLA4) and promotion of Th17 cells. Co-stimulatory independence of memory T cells was another unforeseen limitation. Learning how to better integrate co-stimulatory targeting with other immunosuppressive agents will be critical for the improvement of long-term graft survival.
机译：简介：关于钙调神经磷酸酶抑制剂对肾毒性的关注，导致人们寻找了用于免疫抑制的新型药物。基于对完全活化的初生T细胞的T细胞共刺激信号的要求，很明显，阻断这些途径可能是有吸引力的治疗靶标。然而，在最近的贝拉西普临床试验中发现了一些出乎意料的发现，包括更高的排斥率，这使得有必要对进一步的研究进行进一步的研究，并提出一些有趣的概念。涵盖的领域：本文旨在回顾B7：CD28联合刺激性移植的文献，包括其发展，临床应用和潜在局限性的基本免疫学。专家意见：由于各种共刺激途径之间以及各种共抑制途径之间的相互作用，靶向共刺激途径比最初预期的要复杂得多。另外，共刺激信号在多种免疫细胞类型中具有不同的作用。因此，用细胞毒性T淋巴细胞抗原4（CTLA4）-Ig靶向CD28配体可能具有某些有害作用，包括抑制调节性T细胞，阻断共抑制信号（CTLA4）和促进Th17细胞。记忆T细胞的共同刺激独立性是另一个无法预料的局限性。学习如何更好地将共刺激靶向与其他免疫抑制剂整合在一起对于延长移植物的长期存活至关重要。

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