Abstract
How CD4-CD8 differentiation is maintained in mature T cells is largely unknown. The present study has examined the role in this process of the zinc finger protein Zbtb7b, a critical factor for the commitment of MHC II-restricted thymocytes to the CD4+ lineage. We showed that Zbtb7b acted in peripheral CD4+ T cells to suppress CD8-lineage gene expression, including that of CD8 and cytotoxic effector genes perforin and Granzyme B, and was important for the proper repression of interferon-gamma (IFN-gamma) during effector differentiation. The inappropriate expression of IFN-gamma by Zbtb7b-deficient CD4+ T cells required the activities of Eomesodermin and Runx transcription factors. Runx activity was needed for Granzyme B expression, indicating that Runx proteins control expression of the cytotoxic program. We conclude that a key function of Zbtb7b in the mature CD4+ T cell compartment is to repress CD8-lineage gene expression.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Lineage / genetics*
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Cell Lineage / immunology
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Core Binding Factor Alpha 3 Subunit / immunology
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Core Binding Factor Alpha 3 Subunit / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation / immunology*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Transcription Factors / deficiency
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Transcription Factors / genetics*
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Transcription Factors / immunology
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Transcription Factors / metabolism*
Substances
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Core Binding Factor Alpha 3 Subunit
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DNA-Binding Proteins
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Runx3 protein, mouse
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Transcription Factors
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Zbtb7b protein, mouse