生物
效应器
免疫系统
自身免疫
免疫学
自身抗体
自身免疫性疾病
系统性红斑狼疮
组蛋白
基因
癌症研究
细胞生物学
抗体
遗传学
疾病
内科学
医学
作者
Jesús M. Salvador,M. Christine Hollander,Anh Nguyen,Jeffrey B. Kopp,Laura Barisoni,Jodene K. Moore,Jonathan D. Ashwell,Albert J. Fornace
出处
期刊:Immunity
[Elsevier]
日期:2002-04-01
卷期号:16 (4): 499-508
被引量:187
标识
DOI:10.1016/s1074-7613(02)00302-3
摘要
This study addresses the biological function of the p53-effector genes Gadd45a and p21 in the immune system. We find that Gadd45a is a negative regulator of T cell proliferation because, compared to wild-type cells, Gadd45a(-/-) T cells have a lower threshold of activation and proliferate to a greater extent following primary T cell receptor stimulation. Gadd45a(-/-) mice develop an autoimmune disease, similar to human systemic lupus erythematosus (SLE), characterized by high titers of anti-dsDNA, anti-ssDNA, and anti-histone autoantibodies, severe hematological disorders, autoimmune glomerulonephritis, and premature death. Here we show that the lack of both Gadd45a and p21 dramatically accelerates the development of autoimmunity observed in each individual single-gene disruption mutant, demonstrating that these genes play nonredundant roles in the immune response.
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