A splice variant of the TCR ζ mRNA lacking exon 7 leads to the down-regulation of TCR ζ, the TCR/CD3 complex, and IL-2 production in systemic lupus erythematosus T cells

Kensei Tsuzaka, Yumiko Setoyama, Keiko Yoshimoto, Kiyono Shiraishi, Katsuya Suzuki, Tohru Abe, Tsutomu Takeuchi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The reduction or absence of TCR ζ-chain (ζ) 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 ζ mRNA that lacks the 36-bp exon 7 (ζ mRNA/exon 7(-)) and is accompanied by the down-regulation of ζ protein in T cells from SLE patients. In this study, we show that EX7-mutants (MA5.8 cells deficient in ζ protein that have been transfected with ζ mRNA/exon 7(-)) exhibit a reduction in the expression of TCR/CD3 complex and ζ 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 ζ mRNA). Furthermore, real-time PCR analyses demonstrated that ζ mRNA/exon 7(-) in EX7- mutants was easily degraded compared with ζ mRNA by the WT mutants. Pulse-chase experiment showed ζ protein produced by this EX7- mutants was more rapidly decreased compared with the WT mutants. Thus, the lower stability of ζ mRNA/exon 7(-) might also be responsible for the reduced expression of the TCR/CD3 complex, including ζ protein, in SLE T cells.

Original languageEnglish
Pages (from-to)3518-3525
Number of pages8
JournalJournal of Immunology
Volume174
Issue number6
Publication statusPublished - 2005 Mar 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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