T cell responses in calcineurin A alpha-deficient mice
| Autor: | Abul K. Abbas, G. Wiederrecht, Bo Zhang, Dan Ladd, Jianzhu Chen, E Li, Christine E. Seidman, G J Zimmer, E A O'Neill, Frederick W. Alt, J Cryan, Jonathan G. Seidman |
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| Rok vydání: | 1996 |
| Předmět: |
Interleukin 2
Ovalbumin T-Lymphocytes T cell Molecular Sequence Data Immunology Biology Lymphocyte Activation Tacrolimus Interferon-gamma Mice chemistry.chemical_compound Immune system Antigen Cyclosporin a Phosphoprotein Phosphatases medicine Animals Immunology and Allergy Base Sequence Dose-Response Relationship Drug Chimera Calcineurin Stem Cells Proteins Articles Molecular biology DNA-Binding Proteins medicine.anatomical_structure chemistry Ionomycin Cyclosporine Interleukin-2 Calmodulin-Binding Proteins Mitogens Stem cell Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.183.2.413 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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