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.