Altered expression of the T cell receptor-CD3 complex in systemic lupus erythematosus

SLE T cells may play a key role in autoantibody production in SLE B cells. In addition, accumulating evidence has shown that SLE T cells participate in the attack on target cells or tissues through the overproduction of pro-inflammatory cytokines or an increase in cell-to-cell adhesion. Thus, the functional abnormality of SLE T cells appears to be pivotal to an understanding of SLE pathogenesis. Accumulating evidence suggests that potential defects may reside in the proximal signal transduction around the TCR-CD3 complex. We have demonstrated that the expression of TCR ζ chain is significantly decreased in peripheral blood T cells from SLE patients. To explore the mechanism of defective expression of TCR ζ chain, we examined mRNA of TCR ζ, and found that two alternatively spliced variants such as exon 7 (-) and short 3′-UTR are detected in SLE. We review the possible role of the TCR ζ defects in autoimmunity and discuss how the splicing variants lead to downregulated protein expression of TCR ζ chain.