Mountz J D, Zhou T, Su X, Wu J, Cheng J
Department of Medicine, University of Alabama at Birmingham, USA.
Clin Immunol Immunopathol. 1996 Sep;80(3 Pt 2):S2-14. doi: 10.1006/clin.1996.0136.
Activation-induced apoptosis is a primary mechanism for downmodulation of an immune response leading to immune homeostasis and deletion of T cells with specificities which may be harmful. These include deletion of T cells with self-specificities (autospecific) and excessively high affinity for foreign antigen which may lead to an excessively heightened immune response and septic shock. Surface molecules involved in activation-induced apoptosis involve Fas and Fas ligand (FasL), as well as the T-cell receptor (TCR) which modulates the expression and function of these molecules. Fas signaling mechanisms include the hematopoietic cell phosphatase (HCP) and sphingomyelinase, while TCR-signaling mechanisms include Nur77 and fyn kinase and unknown molecules that modulate expression of FasL. Apoptosis signals are further modulated by inhibitors or inducers of apoptosis including Bcl-2, p53, and interleukin-1 beta converting enzyme (ICE). Further understanding of the interaction of these molecules in autoimmune disease may lead to more specific therapies for immunosuppression tailored to the genetic or environmentally induced, activation-induced apoptosis defect in patients.
活化诱导的细胞凋亡是下调免疫反应的主要机制，可导致免疫稳态以及清除具有潜在有害特异性的T细胞。这些有害特异性包括具有自身特异性（自身特异性）的T细胞以及对外源抗原亲和力过高的T细胞，这可能导致免疫反应过度增强和感染性休克。参与活化诱导细胞凋亡的表面分子包括Fas和Fas配体（FasL），以及调节这些分子表达和功能的T细胞受体（TCR）。Fas信号传导机制包括造血细胞磷酸酶（HCP）和鞘磷脂酶，而TCR信号传导机制包括Nur77和fyn激酶以及调节FasL表达的未知分子。细胞凋亡信号进一步受到细胞凋亡抑制剂或诱导剂的调节，包括Bcl-2、p53和白细胞介素-1β转换酶（ICE）。进一步了解这些分子在自身免疫性疾病中的相互作用，可能会为针对患者遗传或环境诱导的、活化诱导的细胞凋亡缺陷的免疫抑制提供更具特异性的治疗方法。
