Benichou Gilles, Gonzalez Bruno, Marino Jose, Ayasoufi Katayoun, Valujskikh Anna
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH , USA.
Front Immunol. 2017 Feb 28;8:170. doi: 10.3389/fimmu.2017.00170. eCollection 2017.
Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through peripheral non-lymphoid tissues. Alloreactive memory T cells are subdivided into different categories based on their origins, phenotypes, and functions. Recipients whose immune systems have been directly exposed to allogeneic major histocompatibility complex (MHC) molecules display high affinity alloreactive memory T cells. In the absence of any prior exposure to allogeneic MHC molecules, endogenous alloreactive memory T cells are regularly generated through microbial infections (heterologous immunity). Regardless of their origin, alloreactive memory T cells represent an essential element of the allograft rejection process and a major barrier to tolerance induction in clinical transplantation. This article describes the different subsets of alloreactive memory T cells involved in transplant rejection and examine their generation, functional properties, and mechanisms of action. In addition, we discuss strategies developed to target deleterious allospecific memory T cells in experimental animal models and clinical settings.
记忆性T细胞的特征在于其低激活阈值、强大的效应功能以及对传统免疫抑制和共刺激阻断的抗性。与初始T细胞不同，记忆性T细胞驻留在外周非淋巴组织中并在其中循环。同种异体反应性记忆性T细胞根据其起源、表型和功能被细分为不同类别。免疫系统直接接触过同种异体主要组织相容性复合体（MHC）分子的受体会表现出高亲和力的同种异体反应性记忆性T细胞。在没有任何先前接触同种异体MHC分子的情况下，内源性同种异体反应性记忆性T细胞会通过微生物感染（异源免疫）定期产生。无论其起源如何，同种异体反应性记忆性T细胞都是同种异体移植排斥过程的一个基本要素，也是临床移植中诱导耐受的一个主要障碍。本文描述了参与移植排斥的同种异体反应性记忆性T细胞的不同亚群，并研究了它们的产生、功能特性和作用机制。此外，我们还讨论了在实验动物模型和临床环境中针对有害的同种异体特异性记忆性T细胞所开发的策略。
