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* Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267;
Division of Hematology/Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45267; and
Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267
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.
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1 This work was supported by National Institutes of Health Grant CA95286 (to L.C.) and American Heart Association-Ohio Valley Affiliate Predoctoral Fellowship 0615213B (to S.A.N.).
2 Address correspondence and reprint requests to Dr. Laura Conforti, Department of Internal Medicine, 231 Albert Sabin Way, University of Cincinnati, Cincinnati, OH 45267-0585. E-mail address: Laura.Conforti{at}uc.edu
3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; [Ca2+]i, intracellular Ca2+ level; Tcm, central memory T cell; Tem, effector memory T cell; IS, immunological synapse; PKC, protein kinase C; SLEDAI, SLE disease activity index; RA, rheumatoid arthritis; SEB, staphylococcal enterotoxin B; MFR, mean fluorescent ratio; HP, holding potential; EC, extracellular; IC, intracellular; C, Caucasian; AA, African American.
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