T cell responses in calcineurin Aα-deficient mice

Abstract

We have created embryonic stem (ES) cells and mice lacking the predominants isoform (α) of the calcineurin A subunit (CNAα) to study the role of this serine/threonine phosphatase in the immune system. T and B cell maturation appeared to be normal in CNAα(-/-) mice. CNAα(-/-) T cells responded normally to mitogenic stimulation (i.e., PMA plus ionomycin, concanavalin A, and anti-CD3ε antibody). However, CNAα(-/-) mice generated defective antigen-specific T cell responses in vivo. Mice produced from CNAα(-/-) ES cells injected into RAG-2-deficient blastocytes had a similar defective T cell response, indicating that CNAα is required for T cell function per se, rather than for an activity of other cell types involved in the immune response. CNAα(-/-) T cells remained sensitive to both cyclosporin A and FK506, suggesting that CNAβ or another CNA-like molecule can mediate the action of these immunosuppressive drugs. CNA(-/-) mice provide an animal model for dissecting the physiologic functions of calcineurin as well as the effects of FK506 and CsA.