Publication: Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity.
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2001-12
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Cell Press
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Abstract
E2Fs are important regulators of proliferation, differentiation, and apoptosis. Here we characterize the phenotype of mice deficient in E2F2. We show that E2F2 is required for immunologic self-tolerance. E2F2(-/-) mice develop late-onset autoimmune features, characterized by widespread inflammatory infiltrates, glomerular immunocomplex deposition, and anti-nuclear antibodies. E2F2-deficient T lymphocytes exhibit enhanced TCR-stimulated proliferation and a lower activation threshold, leading to the accumulation of a population of autoreactive effector/memory T lymphocytes, which appear to be responsible for causing autoimmunity in E2F2-deficient mice. Finally, we provide support for a model to explain E2F2's unexpected role as a suppressor of T lymphocyte proliferation. Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for normal S phase entry, particularly E2F1.
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Cell Cycle Proteins DNA-Binding Proteins Animals Apoptosis Autoimmune Diseases Autoimmunity Cell Division Chimera Clonal Deletion E2F Transcription Factors E2F1 Transcription Factor E2F2 Transcription Factor Gene Expression Regulation Glomerulonephritis, Membranoproliferative H-Y Antigen Humans Immunologic Memory Inflammation Jurkat Cells Lymphocyte Activation Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mutagenesis, Site-Directed Receptors, Antigen, T-Cell Recombinant Fusion Proteins Repressor Proteins S Phase Self Tolerance Splenomegaly T-Lymphocytes Thymus Gland Transcription Factors Transfection
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Immunity . 2001 ;15(6):959-70.