title: Deficiency of forkhead box P3 and cytotoxic T-lymphocyte-associated antigen-4 gene expressions and impaired suppressor function of CD4(+)CD25(+) T cells in patients with autoimmune hepatitis.
abstract: OBJECTIVE
  Recently, forkhead box P3 (Foxp3), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR), and CD28 were identified as the key molecules that control the development and activation of CD4+CD25+ regulatory T cells (T-reg). We investigated the expression pattern of these molecules on T-reg, and investigated the ability of T-reg to produce cytokines in patients with autoimmune hepatitis (AIH).
  
  
  METHODS
  Fifteen patients with AIH and nine healthy patients were included. To determine the frequency of T-reg, a two-color flow cytometry analysis was performed. T-reg were isolated using immunomagnetic beads, and the mRNA levels of Foxp3, CTLA-4, GITR, and CD28 were quantified by real-time polymerase chain reaction (PCR). The ability of T-reg to produce interferon-gamma, interleukin (IL)-10, transforming growth factor-beta, and tumor necrosis factor-alpha after stimulation by OKT3 was evaluated by measuring the levels of mRNA in T-reg by real-time PCR.
  
  
  RESULTS
  The frequency of T-reg was increased in AIH. The mRNA levels of Foxp3 and CTLA-4 were significantly lower in AIH. The ability of T-reg to produce IL-10 was impaired in AIH.
  
  
  CONCLUSIONS
  We speculate that the inferiority of the Foxp3 and CTLA-4 gene expressions on T-reg results in the impaired suppressor function of T-reg, and eventually in the breakdown of self-tolerance.
authors.affiliation: Department of Gastroenterology, Kainan Hospital, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okumura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sato
authors.forename: Taeko
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Hisae
authors.initials: H
authors.lastname: Oshima
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohashi
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hotta
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kakumu