Calcineurin Aalpha plays an exclusive role in TCR signaling in mature but not in immature T cells

• Published in: European journal of immunology Vol. 32; no. 5; pp. 1223 - 1229
• Main Authors: Chan, Vera S F, Wong, Camilla, Ohashi, Pamela S
• Format: Journal Article
• Language: English
• Published: Germany 01.05.2002
• Subjects: Animals; Antigens, Viral - immunology; Calcineurin - deficiency; Calcineurin - genetics; Calcineurin - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation; Cell Division; Clonal Deletion; DNA-Binding Proteins - metabolism; Glycoproteins - immunology; In Vitro Techniques; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Mice; Mice, Knockout; Mice, Transgenic; NFATC Transcription Factors; Nuclear Proteins; Peptide Fragments - immunology; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; T-Lymphocytes - cytology; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Transcription Factors - metabolism; Viral Proteins - immunology
• ISSN: 0014-2980

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.