Fisher G H, Rosenberg F J, Straus S E, Dale J K, Middleton L A, Lin A Y, Strober W, Lenardo M J, Puck J M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-4470, USA.
Cell. 1995 Jun 16;81(6):935-46. doi: 10.1016/0092-8674(95)90013-6.
Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3+CD4-CD8- lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte apoptosis. Each child had defective Fas-mediated T lymphocyte apoptosis associated with a unique, deleterious Fas gene mutation. One mutation appeared to cause a simple loss of function; however, four others had a dominant negative phenotype when coexpressed with normal Fas. Family studies demonstrated the inheritance of the mutant Fas alleles. The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance.
本文描述了五名无亲缘关系的儿童，他们患有一种罕见的自身免疫性淋巴增殖综合征（ALPS），其特征为大量非恶性淋巴结病、自身免疫现象以及TCR-CD3+CD4-CD8-淋巴细胞群体扩大。这些发现提示T淋巴细胞对正常免疫调节机制作出反应的能力存在遗传缺陷，从而促使对淋巴细胞凋亡进行评估。每个儿童都存在Fas介导的T淋巴细胞凋亡缺陷，且与独特的有害Fas基因突变相关。一种突变似乎导致功能简单丧失；然而，另外四种突变在与正常Fas共表达时具有显性负性表型。家族研究证实了突变Fas等位基因的遗传。Fas突变的出现以及ALPS患者中异常的T细胞凋亡提示Fas参与了这种最近才被认识到的淋巴细胞稳态和外周自身耐受紊乱。
