Calcineurin Aalpha plays an exclusive role in TCR signaling in mature but not in immature T cells.
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.
Chan
Vera S F
VS
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Canada.
Wong
Camilla
C
Ohashi
Pamela S
PS
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019703:Calcineurin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D017637:Clonal Deletion; D004268:DNA-Binding Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D007371:Interferon-gamma; D019703:Calcineurin