Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris

Hayato Takahashi, Masayuki Amagai, Takeji Nishikawa, Yoshiko Fujii, Yutaka Kawakami, Masataka Kuwana

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Autoreactive T cells are thought to be involved in the pathogenesis of autoimmune diseases, but evidence for their direct pathogenicity is almost lacking. Herein we established a unique system for evaluating the in vivo pathogenicity of desmoglein 3 (Dsg3)-reactive T cells at a clonal level in a mouse model for pemphigus vulgaris (PV), an autoimmune blistering disease induced by anti-Dsg3 autoantibodies. Dsg3-reactive CD4+ T cell lines generated in vitro were adoptively transferred into Rag-2-/- mice with primed B cells derived from Dsg3-immunized Dsg3-/- mice. Seven of 20 T cell lines induced IgG anti-Dsg3 Ab production and acantholytic blister, a typical disease phenotype, in recipient mice. Comparison of the characteristics between pathogenic and nonpathogenic Dsg3-reactive T cell lines led to the identification of IL-4 and IL-10 as potential factors associated with pathogenicity. Further in vitro analysis showed that IL-4, but not IL-10, promoted IgG anti-Dsg3 Ab production by primed B cells. Additionally, adenoviral expression of soluble IL-4Rα in vivo suppressed IgG anti-Dsg3 Ab production and the PV phenotype, indicating a pathogenic role of IL-4. This strategy is useful for evaluating the effector function of autoreactive T cells involved in the pathogenesis of various autoimmune diseases.

Original languageEnglish
Pages (from-to)1526-1535
Number of pages10
JournalJournal of Immunology
Volume181
Issue number2
DOIs
Publication statusPublished - 2008 Jul 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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