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PMID: 8627154 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

T cell responses in calcineurin A alpha-deficient mice.

The Journal of experimental medicine ·Vol. 183 ·No. 2 ·1996-02-01 ·Pages 413-20

Zhang BW, Zimmer G, Chen J, Ladd D, Li E, Alt FW, Wiederrecht G, Cryan J, O'Neill EA, Seidman CE, Abbas AK, Seidman JG

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.

MeSH Terms
Animals Base Sequence Calcineurin Calmodulin-Binding Proteins/deficiency,genetics,metabolism Chimera Cyclosporine/pharmacology DNA-Binding Proteins Dose-Response Relationship, Drug Immunosuppressive Agents/pharmacology Interferon-gamma/metabolism Interleukin-2/metabolism Lymphocyte Activation Mice Mitogens/pharmacology Molecular Sequence Data Ovalbumin/immunology Phosphoprotein Phosphatases/deficiency,genetics,metabolism Proteins/genetics Stem Cells T-Lymphocytes/immunology Tacrolimus/pharmacology
Chemicals
Calmodulin-Binding Proteins DNA-Binding Proteins Immunosuppressive Agents Interleukin-2 Mitogens Proteins Rag2 protein, mouse V(D)J recombination activating protein 2 trinitrophenyl-ovalbumin Interferon-gamma Cyclosporine Ovalbumin Calcineurin Phosphoprotein Phosphatases Tacrolimus
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zhang B W
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Zimmer G
Chen J
Ladd D
Li E
Alt F W
Wiederrecht G
Cryan J
O'Neill E A
Seidman C E
Abbas A K
Seidman J G
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.2.413
Published
1996-02-01
Pages
413-20
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192457
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.2.413 PMC Full Text View journal details
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