The Role of Regulatory T Cells in the Pathogenesis of Murine Lupus
Date Issued
2004
Date
2004
Author(s)
Hsu, Wei-Ting
DOI
zh-TW
Abstract
Recent studies have suggested that the dysfunction of regulatory T cells might play a critical role in the pathogenesis of autoimmune diseases. A subset of thymus-derived CD4+ cells that constitutively express CD25 exhibits immune suppressive activity. Depletion of CD4+CD25+ T cells has been shown to cause organ-specific autoimmune diseases. Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the production of antibodies to components of the cell nucleus. At present, it is unknown if regulatory T (Treg) cells are involved in the pathogenesis of SLE. In order to address this question, we assayed the frequency of CD4+CD25+ T cells and measured the related gene expression levels in CD4+CD25+ T cells isolated from both lupus mice (NZB/NZW F1) and normal mice (DBA2/NZW F1). The data showed that the frequency of CD4+CD25+ T cells in young lupus mice was lower than that in normal mice. But in old mice, the frequency of CD4+CD25+ T cells increased and was even higher than that in age matched normal mice. Nucleosome-specific T cells can also be detected in young lupus mice. Therefore, we proposed that the imblalance of regulatory T cells in lupus mice might cause the development of this disease. Furthermore, the Foxp3 and TGF-beta expression of CD4+CD25+ T cells were very similar between both groups of mice. In contrast, the IL-10 expression of CD4+CD25+ T cells isolated from lupus mice was higher than that of normal mice. In in vitro suppression assays, CD4+CD25+ T cells of lupus mice were found to exert suppressive activities as well. Further, we depleted CD4+CD25+ T cells with anti-CD25 antibodies in non-autoimmune mice and broke the tolerance with dendritic cells pulsed with apoptotic cells for the follow up of autoantibody levels. We found that the mice depleted CD4+CD25+ T cells had higher titer of auto-anti-ds/ss DNA antibodies compared with that of control groups. The finding indicated that CD4+CD25+ T cell activities might be involved in the regulating mechanism of autoantibody production. Although more studies are needed, CD4+CD25+ T cells might play a critical role in the regulation of autoimmune response in murine lupus.
Subjects
紅斑性狼瘡
調節性T細胞
狼瘡小鼠
SLE
regulatory T cell
BWF1
Type
other
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