Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Immunotherapy. 2009 May;1(3):385-401. doi: 10.2217/imt.09.2.
Regulatory T cells (Tregs) maintain immunological homeostasis and prevent autoimmunity. The depletion or functional alteration of Tregs may lead to the development of autoimmune diseases. Tregs consist of different subpopulations of cells, of which CD4(+)CD25(+)Foxp3(+) cells are the most well characterized. However, CD8 Tregs also constitute a major cell population that has been shown to play an important role in autoimmune diseases. This review will discuss the role of Tregs in autoimmune diseases in general and specifically in systemic lupus erythematosus (SLE). SLE is a multisystem autoimmune disease characterized by the production of autoantibodies against nuclear components and by the deposition of immune complexes in the kidneys as well as in other organs. Abnormalities in Tregs were reported in SLE patients and in animal models of the disease. Current treatment of SLE is based on immunosuppressive drugs that are nonspecific and may cause adverse effects. Therefore, the development of novel, specific, side effect-free therapeutic means that will induce functional Tregs is a most desirable goal. Our group and others have designed and utilized tolerogenic peptides that ameliorate SLE manifestations in murine models. Here, we demonstrate the role of CD4 and CD8 Tregs, as well as the interaction between the two subsets of cells and the mechanism of action of the tolerogenic peptides. We also discuss their therapeutic potential for the treatment of SLE.
调节性 T 细胞（Tregs）维持着免疫稳态，防止自身免疫。Tregs 的耗竭或功能改变可能导致自身免疫性疾病的发生。Tregs 由不同的细胞亚群组成，其中 CD4(+)CD25(+)Foxp3(+)细胞是最具特征的。然而，CD8 Tregs 也是一个主要的细胞群体，已经证明它在自身免疫性疾病中发挥着重要作用。本综述将讨论 Tregs 在一般自身免疫性疾病中的作用，特别是在系统性红斑狼疮（SLE）中的作用。SLE 是一种多系统自身免疫性疾病，其特征是产生针对核成分的自身抗体，并在肾脏以及其他器官中沉积免疫复合物。SLE 患者和疾病动物模型中报告了 Tregs 的异常。目前 SLE 的治疗基于免疫抑制药物，但这些药物是非特异性的，可能会引起不良反应。因此，开发新型、特异、无副作用的诱导功能性 Tregs 的治疗手段是一个非常理想的目标。我们的研究小组和其他研究小组设计并利用了耐受原性肽，这些肽在小鼠模型中改善了 SLE 的表现。在这里，我们展示了 CD4 和 CD8 Tregs 的作用，以及这两个细胞亚群之间的相互作用以及耐受原性肽的作用机制。我们还讨论了它们在治疗 SLE 方面的治疗潜力。
