Reduced expression of TCR zeta is involved in the abnormal production of cytokines by peripheral T cells of patients with systemic lupus erythematosus

Abstract

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN- in vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN- by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN- by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN- were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE. © 2010 Keiko Yoshimoto et al.