Abnormal Early TCR/CD3-Mediated Signaling Events of a snRNP-Autoreactive Lupus T Cell Clone

Abstract

Multiple immunoregulatory abnormalities characterize systemic lupus erythematosus. Abnormalities of the antigen receptor-mediated early signal transduction biochemical events underscore the diverse cellular aberrations. Fresh peripheral T and B cells and T cell lines from patients with systemic lupus erythematosus display increased Ca²⁺responses that are preceded by enhanced antigen receptor-initiated cytosolic protein tyrosine phosphorylation. To further dissect the aberrant signaling events of lupus T cells we studied the early anti-CD3 mAb-induced signaling events in autoantigen-specific T cells from lupus patients. We report herein that a lupus snRNP-specific T cell clone, but not other T cells, displays increased Ca²⁺fluxes and enhanced production of tyrosine-phosphorylated proteins following TCR/CD3 stimulation.