| Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus. | |
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MedLine Citation:
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PMID: 17579055 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aberrant T cell responses during T cell activation and immunological synapse (IS) formation have been described in systemic lupus erythematosus (SLE). Kv1.3 potassium channels are expressed in T cells where they compartmentalize at the IS and play a key role in T cell activation by modulating Ca(2+) influx. Although Kv1.3 channels have such an important role in T cell function, their potential involvement in the etiology and progression of SLE remains unknown. This study compares the K channel phenotype and the dynamics of Kv1.3 compartmentalization in the IS of normal and SLE human T cells. IS formation was induced by 1-30 min exposure to either anti-CD3/CD28 Ab-coated beads or EBV-infected B cells. We found that although the level of Kv1.3 channel expression and their activity in SLE T cells is similar to normal resting T cells, the kinetics of Kv1.3 compartmentalization in the IS are markedly different. In healthy resting T cells, Kv1.3 channels are progressively recruited and maintained in the IS for at least 30 min from synapse formation. In contrast, SLE, but not rheumatoid arthritis, T cells show faster kinetics with maximum Kv1.3 recruitment at 1 min and movement out of the IS by 15 min after activation. These kinetics resemble preactivated healthy T cells, but the K channel phenotype of SLE T cells is identical to resting T cells, where Kv1.3 constitutes the dominant K conductance. The defective temporal and spatial Kv1.3 distribution that we observed may contribute to the abnormal functions of SLE T cells. |
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Authors:
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Stella A Nicolaou; Peter Szigligeti; Lisa Neumeier; Susan Molleran Lee; Heather J Duncan; Shashi K Kant; Anne Barbara Mongey; Alexandra H Filipovich; Laura Conforti |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 179 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-20 Completed Date: 2007-08-07 Revised Date: 2013-03-07 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 346-56 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antigen-Presenting Cells / immunology*, metabolism, pathology Calcium Signaling / immunology Cell Communication / immunology* Female G0 Phase / immunology Gene Rearrangement, T-Lymphocyte Homeostasis / immunology Humans Immunophenotyping Kinetics Kv1.3 Potassium Channel / biosynthesis, metabolism*, physiology Lupus Erythematosus, Systemic / immunology*, metabolism*, pathology Lymphocyte Activation / immunology Male Middle Aged Protein Binding / immunology Protein Transport / immunology Receptors, Antigen, T-Cell / genetics, metabolism T-Lymphocyte Subsets / immunology*, metabolism, pathology |
| Grant Support | |
ID/Acronym/Agency:
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CA 95286/CA/NCI NIH HHS; R01 CA095286-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Kv1.3 Potassium Channel; 0/Receptors, Antigen, T-Cell |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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