Systemic lupus erythematosus (SLE) T cells exhibit several activation signaling anomalies including defective Ca2+ response and increased NF-AT nuclear translocation. The duration of the Ca2+ signal is critical in the activation of specific transcription factors and a sustained Ca2+ response activates NF-AT. Yet, the distribution of Ca2+ responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca2+ alterations are not fully understood. Kv1.3 channels control Ca2+ homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca2+ defect. The present study compares single T cell quantitative Ca2+ responses upon formation of the IS in SLE, normal, and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca2+ concentrations and Kv1.3 trafficking in the IS by two-photon microscopy. We found that sustained [Ca2+]i elevations constitute the predominant response to antigen stimulation of SLE T cells. This defect is selective to SLE as it was not observed in RA T cells. Further, we observed that in normal T cells termination of Ca2+ influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca2+ responses in SLE T cells. Thus, we propose that Kv1.3 trafficking abnormalities contribute to the altered distribution in Ca2+ signaling in SLE T cells. Overall these defects may explain in part the T cell hyperactivity and dysfunction documented in SLE patients.
- Systemic lupus erythematosus
- T cells