Ni Choileain Niamh, Redmond H P
Department of Surgery, Cork University Hospital, Wilton, Cork, Ireland.
J Surg Res. 2006 Jan;130(1):124-35. doi: 10.1016/j.jss.2005.07.033. Epub 2005 Sep 8.
Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.
大约20%的人口受由异常免疫反应介导的自身免疫性或炎症性疾病影响。自身免疫性疾病的一个特征是某些自身反应性T细胞群体对单一细胞类型、器官或组织的选择性靶向作用。此类疾病的例子包括类风湿性关节炎、胰岛素依赖型糖尿病和系统性红斑狼疮(SLE),所有这些疾病的特征都是慢性炎症、组织破坏和靶器官功能障碍。尽管有确凿证据将大多数自身免疫性疾病与特定基因联系起来,但关于调节性T细胞群体在疾病过程中的作用仍存在相当大的争议。现在人们还认为这些细胞在介导移植耐受和抑制肿瘤免疫诱导中起关键作用。尽管旨在治疗自身免疫性病理的治疗性免疫调节概念已在许多动物模型中得到验证,但治疗人类自身免疫性疾病的策略仍处于起步阶段。这方面的主要障碍包括不同模型系统的相互矛盾的研究结果,以及调节性T细胞和参与此类疾病发展的细胞因子的不同功能。本综述探讨了调节性T细胞在自身免疫发病机制中的作用,并描述了这些细胞未来在预防免疫介导性病理方面的治疗潜力。尽管关于此类病理仍有许多有待了解之处,但对调节性T细胞发挥功能的机制有更清晰的认识无疑将为免疫治疗带来令人兴奋的新可能性。