T cell responses in calcineurin A alpha-deficient mice - PubMed (original) (raw)

. 1996 Feb 1;183(2):413-20.

doi: 10.1084/jem.183.2.413.

G Zimmer, J Chen, D Ladd, E Li, F W Alt, G Wiederrecht, J Cryan, E A O'Neill, C E Seidman, A K Abbas, J G Seidman

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T cell responses in calcineurin A alpha-deficient mice

B W Zhang et al. J Exp Med. 1996.

Abstract

We have created embryonic stem (ES) cells and mice lacking the predominant isoform (alpha) of the calcineurin A subunit (CNA alpha) to study the role of this serine/threonine phosphatase in the immune system. T and B cell maturation appeared to be normal in CNA alpha -/- mice. CNA alpha -/- T cells responded normally to mitogenic stimulation (i.e., PMA plus ionomycin, concanavalin A, and anti-CD3 epsilon antibody). However, CNA alpha -/- mice generated defective antigen-specific T cell responses in vivo. Mice produced from CNA alpha -/- ES cells injected into RAG-2-deficient blastocysts had a similar defective T cell response, indicating that CNA alpha is required for T cell function per se, rather than for an activity of other cell types involved in the immune response. CNA alpha -/- T cells remained sensitive to both cyclosporin A and FK506, suggesting that CNA beta or another CNA-like molecule can mediate the action of these immunosuppressive drugs. CNA alpha -/- mice provide an animal model for dissecting the physiologic functions of calcineurin as well as the effects of FK506 and CsA.

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References

    1. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4528-32 - PubMed
    1. Curr Opin Immunol. 1992 Oct;4(5):548-52 - PubMed
    1. EMBO J. 1994 Feb 15;13(4):861-70 - PubMed
    1. J Immunol. 1994 Mar 1;152(5):2172-9 - PubMed
    1. Mol Biol Cell. 1994 Jan;5(1):119-28 - PubMed

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