Lenardo M, Chan K M, Hornung F, McFarland H, Siegel R, Wang J, Zheng L
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Annu Rev Immunol. 1999;17:221-53. doi: 10.1146/annurev.immunol.17.1.221.
Apoptosis of mature T lymphocytes preserves peripheral homeostasis and tolerance by countering the profound changes in the number and types of T cells stimulated by diverse antigens. T cell apoptosis occurs in at least two major forms: antigen-driven and lymphokine withdrawal. These forms of death are controlled in response to local levels of IL-2 and antigen in a feedback mechanism termed propriocidal regulation. Active antigen-driven death is mediated by the expression of death cytokines such as FasL and TNF. These death cytokines engage specific receptors that assemble caspase-activating protein complexes. These signaling complexes tightly regulate cell death but are vulnerable to inherited defects. Passive lymphokine withdrawal death may result from the cytoplasmic activation of caspases that is regulated by mitochondria and the Bcl-2 protein. The human disease, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fas/APO-1/CD95 receptor and other components of the death pathway. The study of ALPS patients reveals the necessity of apoptosis for preventing autoimmunity and allows the genetic investigation of apoptosis in humans. Immunological, cellular, and molecular evidence indicates that throughout the life of a T cell, apoptosis may be evoked in excessive, harmful, or useless clonotypes to preserve a healthy and balanced immune system.
成熟T淋巴细胞的凋亡通过对抗由多种抗原刺激引起的T细胞数量和类型的深刻变化，维持外周稳态和耐受性。T细胞凋亡至少以两种主要形式发生：抗原驱动型和细胞因子撤离型。这些死亡形式通过一种称为自毁调节的反馈机制，根据局部白细胞介素-2和抗原水平受到调控。活跃的抗原驱动型死亡由FasL和TNF等死亡细胞因子的表达介导。这些死亡细胞因子与特定受体结合，组装激活半胱天冬酶的蛋白复合物。这些信号复合物严格调控细胞死亡，但易受遗传缺陷影响。被动的细胞因子撤离型死亡可能源于由线粒体和Bcl-2蛋白调控的半胱天冬酶的细胞质激活。人类疾病自身免疫性淋巴增殖综合征（ALPS）是由于Fas/APO-1/CD95受体及死亡途径的其他成分发生显性干扰突变所致。对ALPS患者的研究揭示了凋亡对于预防自身免疫的必要性，并使得对人类凋亡进行遗传学研究成为可能。免疫学、细胞和分子证据表明，在T细胞的整个生命周期中，凋亡可能在过度、有害或无用的克隆型中被诱发，以维持健康和平衡的免疫系统。
