Requirement of calcineurin Aβ for the survival of naive T cells

Calcineurin (Cn) is a Ca²⁺/calmodulin-dependent phosphatase that dephosphorylates and activates NFAT, a transcription factor essential for T cell activation. T lymphocytes predominantly express the calcineurin Aβ (CnAβ) isoform, and the deletion of the CnAβ gene results in defective T cell proliferation and IL-2 production in response to TCR stimulation. In this study, we show that CnAβ enhances the spontaneous survival of naive T cells by maintaining high levels of Bcl-2, a critical homeostatic survival factor for naive T cells. T cells obtained from CnAβ^-/- mice displayed accelerated spontaneous apoptosis. The observed apoptosis of the CnAβ^-/- T cells was prevented by IL-7 and IL-15, two cytokines critical for the homeostatic survival of naive T cells. Furthermore, CD4 ⁺ or CD8⁺ single positive CnAβ^-/- thymocytes also underwent accelerated apoptosis. However, no obvious difference in the apoptosis of CD4⁺CD8⁺ double positive thymocytes was observed between CnAβ^-/-and wild-type mice, suggesting a specific function of CnA⁺ in the survival of single positive T cells. Bcl-2 levels were found to be significantly lower in CnAβ^-/- T cells. Transgenic expression of Bcl-x_L restored the survival of the CnAβ^-/- T cells. Thus, in addition to its role in mediating TCR signals essential for T cell activation, CnAβ is also required for the homeostatic survival of naive T cells.