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mRNA Lacking Exon 7 Leads to the Down-Regulation of TCR , the TCR/CD3 Complex, and IL-2 Production in Systemic Lupus Erythematosus T Cells1
* Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Saitama, Japan; and
Research Center for Genomic Medicine, Saitama Medical School, Hidaka, Saitama, Japan
The reduction or absence of TCR 
-chain () expression in patients with systemic lupus erythematosus (SLE) is thought to be a factor in the pathogenesis of SLE. We previously reported a splice variant of mRNA that lacks the 36-bp exon 7 ( mRNA/exon 7(–)) and is accompanied by the down-regulation of protein in T cells from SLE patients. In this study, we show that EX7– mutants (MA5.8 cells deficient in protein that have been transfected with mRNA/exon 7(–)) exhibit a reduction in the expression of TCR/CD3 complex and protein on their cell surface as well as a reduction in the production of IL-2 after stimulation with anti-CD3 Ab, compared with that in wild-type (WT) mutants (MA5.8 cells transfected with the WT mRNA). Furthermore, real-time PCR analyses demonstrated that mRNA/exon 7(–) in EX7– mutants was easily degraded compared with mRNA by the WT mutants. Pulse-chase experiment showed protein produced by this EX7– mutants was more rapidly decreased compared with the WT mutants. Thus, the lower stability of mRNA/exon 7(–) might also be responsible for the reduced expression of the TCR/CD3 complex, including protein, in SLE T cells.
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