Altered Dynamics of Kv1.3 Channel Compartmentalization in the Immunological Synapse in Systemic Lupus Erythematosus

• Published in: Journal of Immunology 2007-07, Vol.179 (1), p.346-356
• Main Authors: Nicolaou, Stella A, Szigligeti, Peter, Neumeier, Lisa, Molleran Lee, Susan, Duncan, Heather J, Kant, Shashi K, Mongey, Anne Barbara, Filipovich, Alexandra H, Conforti, Laura
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigen-Presenting Cells - pathology; Calcium Signaling - immunology; Cell Communication - immunology; Female; Gene Rearrangement, T-Lymphocyte; Homeostasis - immunology; Humans; Immunophenotyping; Kinetics; Kv1.3 Potassium Channel - biosynthesis; Kv1.3 Potassium Channel - metabolism; Kv1.3 Potassium Channel - physiology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation - immunology; Male; Middle Aged; Protein Binding - immunology; Protein Transport - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Resting Phase, Cell Cycle - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.1.346

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.