Viglietta Vissia, Baecher-Allan Clare, Weiner Howard L, Hafler David A
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Exp Med. 2004 Apr 5;199(7):971-9. doi: 10.1084/jem.20031579.
CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.
CD4+CD25+调节性T细胞通过主动抑制作用有助于维持外周免疫耐受，因为它们的缺失会在小鼠中引发自发性自身免疫疾病。表达高水平CD25的人CD4+调节性T细胞在体外具有抑制作用，并模拟小鼠CD4+CD25+调节性T细胞的活性。多发性硬化症（MS）是一种炎症性疾病，被认为是由识别髓鞘蛋白肽的T细胞介导的。我们假设CD4+CD25hi调节性T细胞功能的改变在MS患者免疫自身耐受的破坏中起作用。在此，我们报告与健康供体相比，MS患者外周血中CD4+CD25hi调节性T细胞的效应功能显著降低。在单细胞克隆实验中差异也很明显，与正常对照相比，患者中CD4+CD25hi T细胞的克隆频率显著降低。这些数据首次证明了MS患者中CD4+CD25hi调节性T细胞功能的改变。
