Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus.
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.
Nicolaou
Stella A
SA
Department of Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Szigligeti
Peter
P
Neumeier
Lisa
L
Lee
Susan Molleran
SM
Duncan
Heather J
HJ
Kant
Shashi K
SK
Mongey
Anne Barbara
AB
Filipovich
Alexandra H
AH
Conforti
Laura
L
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D051664:Kv1.3 Potassium Channel / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D051664:Kv1.3 Potassium Channel; D011948:Receptors, Antigen, T-Cell