Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus

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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Abstract

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)346-356
Number of pages11
JournalJournal of Immunology
Volume179
Issue number1
Publication statusPublished - 1 Jul 2007

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    Nicolaou, S. A., Szigligeti, P., Neumeier, L., Lee, S. M., Duncan, H. J., Kant, S. K., Mongey, A. B., Filipovich, A. H., & Conforti, L. (2007). Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus. Journal of Immunology, 179(1), 346-356.