The Role of Regulatory T cells in the Immune Modulation of Disease Activity in Murine Lupus
Date Issued
2005
Date
2005
Author(s)
Hsu, Chia-Lin
DOI
en-US
Abstract
Systemic lupus erythematosus (SLE) is a multiple organic autoimmune disease, which caused by has many pathogenic factors including defect in regulation of autoreactive lymphocytes. In the first part of the study, we aimed to study whether regulatory T cells could alleviate disease severity of lupus. Foxp3, a forkhead transcription factor, specifically expressed in CD4+CD25+ regulatory T cells (Treg) is a key regulatory gene for development and function of Treg. Foxp3-transfected CD4+CD25- T cells have immunosuppressive function as nature occurring CD4+CD25+ regulatory T cells. It has been well known that Treg have suppressive function and can control several immune responses caused by self or non-self antigens. In this study, we like to investigate if we can deliver the Foxp3-overexpressed T cells for the alleviation of disease severity in murine lupus.
We first isolated CD4+CD25+ T cells isolated from nonautoimmune DBA2/NZW F1 mice and adoptively transferred to NZB/NZW F1 mice, which spontaneously develop lupus. By assaying antibodies against dsDNA and ssDNA, we found that these cells could decrease the level of autoantibodies comparing to control mice. The therapeutic effects were seen one month after transfer, and could sustain for three months. We further wanted to induce regulatory T cells by infected CD4+CD25- T cells with Foxp3-expressing lentivirus. We have concentrated the lentivirus vector expressing Foxp3 gene, however, the in vivo study is yet to be finished.
In the second part of the study, we would like to know whether arsenic trioxide (As2O3), a well known anticancer agent, could alleviate disease severity of SLE. We intraperitoneally injected different dose of arsenic trioxide to NZB/NZW F1 mice three days a week for two months. It was found that, one month after injection of arsenic trioxide the level of autoantibodies was lowered comparing to mice of control group. And the percentage of severe glomerulonephritis (GN) was lower in treatment groups. In addition, mice injected with arsenic trioxide were lived longer than mice injected with PBS only.
Both adoptive transfers of CD4+CD25+ regulatory T cells and treatment of arsenic trioxide could alleviate the disease severity in lupus mice. In the future, these therapeutic approaches may be applied to clinical purposes.
Subjects
調節
狼瘡
免疫
regulatory T cell
lupus
SDGs
Type
other
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