CD4(+) CD25(+) regulatory T cells ameliorate Behcet's disease-like symptoms in a mouse model.

Abstract

Behcet's disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic, gastrointestinal, mucocutaneous, ocular, vascular and central nervous system involvement. It is well known that CD4(+) CD25(+) T-regulatory (Treg) cells prevent harmful immune responses to self- and non-self-antigens. In the present study, the role of Treg cells in herpes simplex virus (HSV)-induced BD-like symptoms was investigated. HSV type 1 (F strain) inoculation of the earlobe of ICR mice has been shown to induce the development of BD-like symptoms. To determine whether the effect of Treg was associated with change in BD-like symptoms, CD4(+) CD25(+) T cells from the splenocytes of normal mice were adoptively transferred intravenously. Treg cells of splenocytes were significantly elevated following the transfer of 3 × 10(5) CD4(+) CD25(+) T cells to BD-like mice compared with the control group. The transfer of CD4(+) CD25(+) T cells to BD mice improved the symptoms, and the serum protein levels of interleukin (IL)-10, IL-6 and IL-17 were significantly altered compared with the control groups. Intravenous injection of anti-CD25 antibody to BD mice reduced the frequency of CD4(+) CD25(+) T cells and increased the BD severity score. We confirmed the influence of CD4(+) CD25(+) T cells on BD-like mice. These results show that up-regulation of the CD4(+) CD25(+) T cells in BD-like mice improves the inflammatory symptoms, while down-regulation of CD25(+) T cells is associated with deteriorated symptoms. Furthermore, these findings are correlated with changes in pro-inflammatory and anti-inflammatory cytokine levels.