Abstract
Calcineurin has been demonstrated as one of the key enzymes in TCR-mediated signaling cascades that lead to the transcription of a variety of cytokines including IL-2. In this study, we addressed the role of calcineurin in lymphocyte development and peripheral T cell responses using the lymphocytic choriomeningitis virus glycoprotein peptide p33-specific, TCR (P14)-transgenic T cells that were deficient in calcineurin subunit A alpha-isoform (CNAalpha(-/-)). Fetal thymic organ culture of P14/CNAalpha(-/-) lobes showed no defect in positive or negative selection of thymocytes. In addition, peptide-induced peripheral T cell deletion was also normal in CNAalpha-deficient T cells. In terms of mature T cell function, a reduction in proliferation, and IL-2 and IFN-gamma production was observed upon stimulation of P14/CNAalpha(-/-) T cells with the antigenic peptide. Impaired NF-AT nuclear localization was also observed. These results suggest that CNAalphais important for mature T cell function, but has a limited role in thymocyte development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Viral / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Calcineurin / deficiency
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Calcineurin / genetics
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Calcineurin / metabolism*
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Cell Differentiation
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Cell Division
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Clonal Deletion
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DNA-Binding Proteins / metabolism
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Glycoproteins / immunology
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In Vitro Techniques
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Interferon-gamma / biosynthesis
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Interleukin-2 / biosynthesis
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Mice
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Mice, Knockout
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Mice, Transgenic
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NFATC Transcription Factors
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Nuclear Proteins*
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Peptide Fragments / immunology
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology*
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Transcription Factors / metabolism
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Viral Proteins / immunology
Substances
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Antigens, Viral
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DNA-Binding Proteins
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Glycoproteins
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Transcription Factors
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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Interferon-gamma
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Calcineurin