Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1064, Nantes, France.
Am J Transplant. 2012 Jul;12(7):1682-90. doi: 10.1111/j.1600-6143.2012.04032.x. Epub 2012 Apr 4.
Tolerance induction to alloantigens remains a major challenge in transplant immunology. Progress in the last decade of our understanding of T-cell activation has led to the development of new immunotherapeutic strategies to replace conventional immunosuppression which inhibits the immune system in a nonspecific way. In particular, positive and negative costimulatory molecules of the CD28 family have been consistently demonstrated to be critical for the development of productive immune responses as well as the establishment and maintenance of peripheral tolerance. However, recent discoveries of novel costimulatory interactions confer a novel dimension to the immunoregulatory interactions within the B7:CD28 family and compels a revised view within a "quintet" of costimulatory molecules: CD28/B7/CTLA-4/PD-L1/ICOSL. Complexity introduced in this more detailed costimulatory pathway has important implications in therapeutic interventions against human immunological diseases and, especially, highlight the fundamental differences in selectively targeting CD28 molecules instead of B7 counterparts. In this review, we discuss these differences and emphasize different CD28-specific immunomodulating strategies evaluated in experimental models of transplantation and autoimmune diseases.
同种异体抗原的耐受诱导仍然是移植免疫学中的一个主要挑战。在过去十年中，我们对 T 细胞激活的理解取得了进展，这导致了新的免疫治疗策略的发展，以取代传统的抑制免疫系统的非特异性免疫抑制。特别是，CD28 家族的正向和负向共刺激分子已被一致证明对于产生有效的免疫反应以及建立和维持外周耐受至关重要。然而，最近发现的新型共刺激相互作用为 B7:CD28 家族内的免疫调节相互作用赋予了新的维度，并迫使人们对“五重奏”共刺激分子（CD28/B7/CTLA-4/PD-L1/ICOSL）进行重新评估。在这个更详细的共刺激途径中引入的复杂性在针对人类免疫性疾病的治疗干预中具有重要意义，尤其是突出了选择性靶向 CD28 分子而不是 B7 对应物的根本区别。在这篇综述中，我们讨论了这些差异，并强调了在移植和自身免疫性疾病的实验模型中评估的不同的 CD28 特异性免疫调节策略。
