Document Detail

Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus.
MedLine Citation:
PMID:  17579055     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  179     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-20     Completed Date:  2007-08-07     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  346-56     Citation Subset:  AIM; IM    
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MeSH Terms
Antigen-Presenting Cells / immunology*,  metabolism,  pathology
Calcium Signaling / immunology
Cell Communication / immunology*
G0 Phase / immunology
Gene Rearrangement, T-Lymphocyte
Homeostasis / immunology
Kv1.3 Potassium Channel / biosynthesis,  metabolism*,  physiology
Lupus Erythematosus, Systemic / immunology*,  metabolism*,  pathology
Lymphocyte Activation / immunology
Middle Aged
Protein Binding / immunology
Protein Transport / immunology
Receptors, Antigen, T-Cell / genetics,  metabolism
T-Lymphocyte Subsets / immunology*,  metabolism,  pathology
Grant Support
CA 95286/CA/NCI NIH HHS; R01 CA095286/CA/NCI NIH HHS; R01 CA095286-05/CA/NCI NIH HHS
Reg. No./Substance:
0/Kv1.3 Potassium Channel; 0/Receptors, Antigen, T-Cell

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