Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris

Kazuyuki Tsunoda, Takayuki Ota, Harumi Suzuki, Manabu Ohyama, Tetsuo Nagai, Takeji Nishikawa, Masayuki Amagai, Shigeo Koyasu

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Mechanisms of tolerance break against desmoglein 3 (Dsg3) in patients with pemphigus vulgaris (PV) producing pathogenic anti-Dsg3 IgG autoantibodies are unclear. In this study, using a novel PV mouse model involving Dsg3 knockout mice, we investigated the mechanisms leading to production of autoantibodies against Dsg3. Adoptive transfer of Dsg3-/- splenocytes immunized with recombinant mouse Dsg3 to Rag2-/- recipient mice expressing Dsg3 resulted in the stable production of anti-Dsg3 IgG and development of PV phenotypes including oral erosions with suprabasilar acantholysis. When purified T and B cells from Dsg3-/-, Dsg3+/- or Dsg3+/+ mice were mixed with various combinations and transferred to Rag2-/- mice, pathogenic anti-Dsg3 IgG production was observed only with a combination of Dsg3-/-T and Dsg3-/- B cells but not with the other combinations. These results suggest that loss of tolerance against Dsg3 in both B and T cells is important for the development of auto-immune state of PV.

Original languageEnglish
Pages (from-to)627-633
Number of pages7
JournalEuropean Journal of Immunology
Volume32
Issue number3
DOIs
Publication statusPublished - 2002 Apr 9

Keywords

  • Autoantibody
  • Disease model
  • Knockout mouse
  • Self tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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