Objective: CD4⁢ T cells from patients with systemic lupus erythematosus (SLE) display aberrant TCR signaling and IFN-α plays critical roles in the pathogenesis of SLE; however, the effects of IFN-α on disease-associated TCR signaling defects remain unknown. This study investigated the ERK phosphorylation during TCR triggering and the effects of IFN-α on ERK signaling in CD4⁢ T cells. Methods: CD4⁢ T lymphocytes were sorted from PBMC using magnetic beads in patients with SLE who met the 1982 revised ACR criteria for SLE and age-matched healthy controls. The phosphorylation of ERK 1/2 was analyzed by flow cytometry and mean fluorescent intensity was measured to define the degree of phosphorylation of ERK. In some experiments, anti-CD3 stimulation was performed after preincubation with patient or control serum, diluted in tissue culture media, with or without addition of an anti-IFN-α antibody. The serum level of IFN-α was measured by ELISA. Results: ERK-1/2 phosphorylation was decreased in CD4⁢ T cells of lupus patients than healthy controls and associated with disease activity. Pre-incubation of control CD4⁢ T cells with allogeneic lupus plasma decreased ERK-1/2 phosphorylation more than allogeneic control and RA plasma and this was reversed by anti-IFN-α Ab. Accordingly, ERK-1/2 phosphorylationwas decreased in control CD4⁢ T cells pre-incubation with lupus plasma with high IFN-α levels more than lupus plasma with non-detectable IFN-α levels. Recombinant IFN-α inhibited TCR-mediated ERK-1/2 phosphorylation dose-dependently. Conclusion: These results suggest that IFN-α stimulation in vivo may underlie the aberrant TCR-mediated MAPK signaling in lupus CD4⁢ T cells and associated with disease pathogenesis.

Keywords: CD4⁢, T cells, ERK signal, IFN-α, Systemic lupus erythematosus