| First Author | Bueno OF | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 14 | Pages | 9398-403 |
| PubMed ID | 12091710 | Mgi Jnum | J:77729 |
| Mgi Id | MGI:2182491 | Doi | 10.1073/pnas.152665399 |
| Citation | Bueno OF, et al. (2002) Defective T cell development and function in calcineurin A beta -deficient mice. Proc Natl Acad Sci U S A 99(14):9398-403 |
| abstractText | The calcium-dependent phosphatase calcineurin and its downstream transcriptional effector nuclear factor of activated T cells (NFAT) are important regulators of inducible gene expression in multiple cell types. In T cells, calcineurin-NFAT signaling represents a critical event for mediating cellular activation and the immune response. The widely used immunosuppressant agents cyclosporin and FK506 are thought to antagonize the immune response by directly inhibiting calcineurin-NFAT signal transduction in lymphocytes. To unequivocally establish the importance of calcineurin signaling as a mediator of the immune response, we deleted the gene encoding the predominant calcineurin isoform expressed in lymphocytes, calcineurin A beta (CnA beta). CnA beta(-/-) mice were viable as adults, but displayed defective T cell development characterized by fewer total CD3 cells and reduced CD4 and CD8 single positive cells. Total peripheral T cell numbers were significantly reduced in CnA beta(-/-) mice and were defective in proliferative capacity and IL-2 production in response to PMA/ionomycin and T cell receptor cross-linking. CnA beta(-/-) mice also were permissive to allogeneic tumor-cell transplantation in vivo, similar to cyclosporin-treated wild-type mice. A mechanism for the compromised immune response is suggested by the observation that CnA beta(-/-) T cells are defective in stimulation-induced NFATc1, NFATc2, and NFATc3 activation. These results establish a critical role for CnA beta signaling in regulating T cell development and activation in vivo. |
