Monti Paolo, Bonifacio Ezio
Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy,
Curr Diab Rep. 2014;14(9):518. doi: 10.1007/s11892-014-0518-9.
Antigen-experienced T-cells directly target and destroy insulin-producing beta cells in patients with Type 1 diabetes. Consequently, T-cells are also major targets of immunomodulatory strategies that aim to prevent or delay the immune mediated loss of islet beta-cell function. These strategies have had modest success, prompting efforts into better defining the mechanisms that drive the differentiation of quiescent autoreactive clones into pathogenic effector and memory T-cells. Recent and novel findings now indicate that in addition to the classic mechanisms of antigenic recognition, autoreactive T-cell differentiation and expansion can be boosted by the homeostatic cytokine interleukin-7. In this article, we discuss recent evidence of the role of IL-7 mediated T-cell proliferation in the pathogenesis of Type 1 diabetes and the rationale for including immunomodulatory molecules targeting the IL-7/IL-7R axis in immunotherapeutic strategies to control beta-cell autoimmunity.
在1型糖尿病患者中，已接触抗原的T细胞直接靶向并破坏产生胰岛素的β细胞。因此，T细胞也是免疫调节策略的主要靶点，这些策略旨在预防或延缓免疫介导的胰岛β细胞功能丧失。这些策略取得了一定的成功，促使人们努力更好地确定驱动静止的自身反应性克隆分化为致病性效应T细胞和记忆T细胞的机制。最近的新发现表明，除了经典的抗原识别机制外，自身反应性T细胞的分化和扩增还可由稳态细胞因子白细胞介素-7促进。在本文中，我们讨论了白细胞介素-7介导的T细胞增殖在1型糖尿病发病机制中的作用的最新证据，以及在免疫治疗策略中纳入靶向白细胞介素-7/白细胞介素-7受体轴的免疫调节分子以控制β细胞自身免疫的基本原理。
