Souffrant Andre, Wilson Avery, Hansen Bryar, Tomofuji Katsuhiro, Otsuka Ryo, Benichou Gilles, Spitzer Thomas, Kawai Tatsuo
Massachusetts General Hospital, Center for Transplantation Sciences, 55 Fruit St., Boston, MA, 02114, USA.
Massachusetts General Hospital, Center for Clinical Transplant Tolerance, 55 Fruit St., Boston, MA, 02114, USA.
Best Pract Res Clin Haematol. 2025 Jun;38(2):101627. doi: 10.1016/j.beha.2025.101627. Epub 2025 May 24.
Transplantation tolerance is an immunologic state in which a transplant recipient's immune system does not mount a destructive immune response to an allograft. Tolerance offers an alternative to lifelong immunosuppression, potentially extending both allograft and patient survival by reducing transplant-related morbidity. Currently, the only clinically relevant approaches to achieve allograft tolerance rely on induction of donor hematopoietic chimerism through bone marrow or hematopoietic cell transplantation. There are two known types of T cell tolerance to alloantigens - central and peripheral. In central tolerance, alloantigen presentation in the thymic medulla results in clonal deletion of alloreactive immature lymphocytes. Peripheral tolerance is mediated by development of tolerogenic cell populations such as immature dendritic cells and regulatory T cells which suppress or delete alloreactive immune cells in the periphery. As the signaling molecules secreted by immune cells to orchestrate immune responses, cytokines are important in development of both central and peripheral tolerance and are critical in mediating both allograft rejection and tolerance. Understanding the immunology underlying the effects of cytokines on the immune system can help us to better understand their role in tolerance and to leverage that understanding to more reliably and safely induce transplantation tolerance.
移植耐受是一种免疫状态，在此状态下移植受者的免疫系统不会对同种异体移植物产生破坏性免疫反应。耐受为终身免疫抑制提供了一种替代方案，通过降低移植相关的发病率，有可能延长同种异体移植物和患者的生存期。目前，实现同种异体移植物耐受的唯一临床相关方法依赖于通过骨髓或造血细胞移植诱导供体造血嵌合体。已知存在两种对同种异体抗原的T细胞耐受类型——中枢性和外周性。在中枢耐受中，胸腺髓质中的同种异体抗原呈递导致同种反应性未成熟淋巴细胞的克隆清除。外周耐受由耐受性细胞群体的发育介导，如未成熟树突状细胞和调节性T细胞，它们在外周抑制或清除同种反应性免疫细胞。作为免疫细胞分泌以协调免疫反应的信号分子，细胞因子在中枢和外周耐受的发展中都很重要，并且在介导同种异体移植物排斥和耐受方面都至关重要。了解细胞因子对免疫系统作用的免疫学基础有助于我们更好地理解它们在耐受中的作用，并利用这一理解更可靠、安全地诱导移植耐受。
