Siegel R M, Fleisher T A
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, and the Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
J Allergy Clin Immunol. 1999 May;103(5 Pt 1):729-38. doi: 10.1016/s0091-6749(99)70412-4.
The Fas receptor, also known as APO-1 or CD95, has emerged as a key initiator of apoptotic programmed cell death in a variety of cell types. CD4(+) T cells are unique in their ability to commit "suicide" by stimulating their own Fas receptors with secreted or membrane-bound Fas ligand. This takes place in the setting of repeated stimulation with T-cell antigens and is thought to be a mechanism for controlling the expansion of T cells during viral infections and autoimmune disease states. T cells can also trigger apoptosis in B cells, macrophages, and other cell types through Fas ligand. These interactions negatively regulate the immune system but can also contribute to immunopathology, as occurs in Fas-mediated damage of target tissues in hepatitis and other organ-specific autoimmune diseases. The dual role of Fas in the immune response complicates the understanding of its role in disease states and may limit its potential as a therapeutic target. Despite the many roles of Fas in immunoregulation, findings in experimental mouse strains and human patients with genetic deficiencies in the Fas pathway have shown that the main result of disrupting this pathway in vivo is systemic autoimmunity and a predisposition toward lymphoid malignancies. The role of Fas in various cell types and the lessons we have learned from Fas-deficient patients with the autoimmune lymphoproliferative syndrome will be discussed.
Fas受体，也被称为APO-1或CD95，已成为多种细胞类型中凋亡程序性细胞死亡的关键启动因子。CD4(+) T细胞具有独特的能力，即通过分泌的或膜结合的Fas配体刺激自身的Fas受体来“自杀”。这发生在T细胞抗原反复刺激的情况下，被认为是在病毒感染和自身免疫疾病状态期间控制T细胞扩增的一种机制。T细胞还可以通过Fas配体触发B细胞、巨噬细胞和其他细胞类型的凋亡。这些相互作用对免疫系统产生负调节作用，但也可能导致免疫病理学，如在肝炎和其他器官特异性自身免疫疾病中Fas介导的靶组织损伤。Fas在免疫反应中的双重作用使人们对其在疾病状态中的作用理解复杂化，并可能限制其作为治疗靶点的潜力。尽管Fas在免疫调节中有多种作用，但在实验小鼠品系和Fas途径存在基因缺陷的人类患者中的研究结果表明，在体内破坏该途径的主要结果是全身性自身免疫和易患淋巴恶性肿瘤。本文将讨论Fas在各种细胞类型中的作用以及我们从患有自身免疫性淋巴增生综合征的Fas缺陷患者身上学到的经验教训。
