DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME

被引：1228

作者：

FISHER, GH

ROSENBERG, FJ

STRAUS, SE

DALE, JK

MIDDELTON, LA

LIN, AY

STROBER, W

LENARDO, MJ

PUCK, JM

机构：

[1] NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892

[2] NIAID,IMMUNOL LAB,BETHESDA,MD 20892

[3] NIAID,CLIN INVEST LAB,BETHESDA,MD 20892

[4] NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892

[5] NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892

来源：

CELL | 1995年 / 81卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/0092-8674(95)90013-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：935 / 946

页数：12

共 56 条

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