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
Article first published online: 4 JUL 2008
© 2008 The Japan Society of Hepatology
Volume 38, Issue 9, pages 896–903, September 2008
How to Cite
Okumura, A., Ishikawa, T., Sato, S., Yamauchi, T., Oshima, H., Ohashi, T., Sato, K., Ayada, M., Hotta, N. and Kakumu, S. (2008), 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. Hepatology Research, 38: 896–903. doi: 10.1111/j.1872-034X.2008.00349.x
- Issue published online: 5 AUG 2008
- Article first published online: 4 JUL 2008
- Received 4 December 2007; revision 20 January 2008; accepted 28 January 2008.
- autoimmune hepatitis;
- CD4+CD25+ regulatory T cells;
- cytotoxic T-lymphocyte-associated antigen-4;
- forkhead box P3;
Aim: 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-γ, interleukin (IL)-10, transforming growth factor-β, and tumor necrosis factor-α 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.
Conclusion: 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.