Podojil Joseph R, Turley Danielle M, Miller Stephen D
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Tarry 6-718, 303 E. Chicago Ave., Chicago, IL 60611, USA.
Adv Exp Med Biol. 2008;640:234-51. doi: 10.1007/978-0-387-09789-3_18.
CD4+ T-cell-mediated autoimmune diseases are initiated and maintained by the presentation of self-antigen by antigen-presenting cells (APCs) to self-reactive CD4+ T-cells. According to the two-signal hypothesis, activation of a naive antigen-specific CD4+ T-cell requires stimulation of both the T-cell antigen receptor (signal 1) and costimulatory molecules such as CD28 (signal 2). To date, the majority of therapies for autoimmune diseases approved by the Food and Drug Administration primarily focus on the global inhibition of immune inflammatory activity. The goal of ongoing research in this field is to develop antigen-specific treatments which block the deleterious effects of self-reactive immune cell function while maintaining the ability of the immune system to clear nonself antigens. To this end, the signaling pathways involved in the induction of CD4+ T-cell anergy, as apposed to activation, are a topic of intense interest. This chapter discusses components of the CD4+ T-cell activation pathway that may serve as therapeutic targets for the treatment of autoimmune disease.
CD4+ T细胞介导的自身免疫性疾病是由抗原呈递细胞（APC）将自身抗原呈递给自身反应性CD4+ T细胞而引发并维持的。根据双信号假说，初始抗原特异性CD4+ T细胞的激活需要T细胞抗原受体（信号1）和共刺激分子如CD28（信号2）的双重刺激。迄今为止，美国食品药品监督管理局批准的大多数自身免疫性疾病疗法主要集中在对免疫炎症活动的全面抑制。该领域正在进行的研究目标是开发抗原特异性治疗方法，在维持免疫系统清除非自身抗原能力的同时，阻断自身反应性免疫细胞功能的有害影响。为此，与激活相反，参与诱导CD4+ T细胞无反应性的信号通路成为了研究热点。本章讨论了CD4+ T细胞激活途径中可能作为自身免疫性疾病治疗靶点的组成部分。
