China-Australia Centre for Personalised Immunology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
Nat Rev Rheumatol. 2019 Aug;15(8):475-490. doi: 10.1038/s41584-019-0254-2. Epub 2019 Jul 9.
As a hallmark of autoimmune rheumatic diseases, autoantibodies have been used in diagnosis for decades. However, the immunological mechanism underlying their generation has only become clear following the identification of T follicular helper (T) cells and T follicular regulatory (T) cells. T cells are instrumental in supporting antibody affinity maturation in germinal centre reactions and humoral memory formation, whereas T cells suppress T cell-mediated antibody responses. Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of T cells that can be hyperactive, and also potentially have altered numbers of T cells with reduced function, suggesting a conceivable dysregulation in the balance between T cells and T cells in these diseases. Therefore, by identifying the molecular mechanisms underlying the development and function of these cell populations, new opportunities have emerged to develop novel therapeutic targets. An increased knowledge of T cells and T cells has inspired, and hopefully will inspire more, approaches to reinstate the balance of these cells in the prevention and treatment of rheumatic diseases.
作为自身免疫性风湿性疾病的标志,自身抗体已被用于诊断数十年。然而,在鉴定滤泡辅助 T(Tfh)细胞和滤泡调节 T(Tfr)细胞之后,其产生的免疫机制才变得清晰。T 细胞在支持生发中心反应中的抗体亲和力成熟和体液记忆形成中起重要作用,而 T 细胞则抑制 T 细胞介导的抗体反应。有证据表明,自身免疫性风湿性疾病患者的 T 细胞数量增加,且可能具有功能降低的 T 细胞数量改变,这表明这些疾病中 T 细胞和 T 细胞之间的平衡可能出现紊乱。因此,通过鉴定这些细胞群体的发展和功能的分子机制,为开发新的治疗靶点提供了新的机会。对 T 细胞和 T 细胞的深入了解激发了,并且有望激发更多的方法来恢复这些细胞在预防和治疗风湿性疾病中的平衡。