Haufe Susanne, Haug Markus, Schepp Carsten, Kuemmerle-Deschner Jasmin, Hansmann Sandra, Rieber Nikolaus, Tzaribachev Nikolay, Hospach Toni, Maier Jan, Dannecker Guenther E, Holzer Ursula
University Children's Hospital Tuebingen, Tuebingen, Germany.
Arthritis Rheum. 2011 Oct;63(10):3153-62. doi: 10.1002/art.30503.
Natural CD4+CD25+FoxP3+ Treg cells play a crucial role in maintaining immune homeostasis and controlling autoimmunity. In patients with juvenile idiopathic arthritis (JIA), inflammation occurs despite the increased total numbers of Treg cells in the synovial fluid (SF) compared to the peripheral blood (PB). This study was undertaken to investigate the phenotype of CD4+ T cells in PB and SF from JIA patients, the function of synovial Treg cells, and the sensitivity of PB and SF CD4+CD25- effector T cells to the immunoregulatory properties of Treg cells, and to study the suppression of cytokine secretion from SF effector T cells by Treg cells.
The phenotypes of effector T cells and Treg cells of PB and SF from JIA patients and healthy donors were determined by flow cytometry. The functionality of isolated Treg cells and effector T cells was quantified in (3) H-thymidine proliferation assays. Cytokine levels were analyzed using Bio-Plex Pro assay.
Compared to PB, SF showed significantly elevated numbers of activated and differentiated CD4+CD45RO+ T cells. Sensitivity of SF effector T cells to the suppressive effects of Treg cells from both PB and SF was impaired, correlating inversely with the expression of CD69 and HLA-DR. However, SF effector T cell cytokine secretion was partly suppressed by SF Treg cells.
Our findings indicate that regulation is impaired in the SF of patients with JIA, as shown by the resistance of effector T cells to immunoregulation by functional Treg cells. This resistance of the SF effector T cells might be due to their activated phenotype.
天然CD4+CD25+FoxP3+调节性T细胞在维持免疫稳态和控制自身免疫中起关键作用。在幼年特发性关节炎（JIA）患者中，尽管与外周血（PB）相比，滑液（SF）中调节性T细胞总数增加，但仍会发生炎症。本研究旨在调查JIA患者PB和SF中CD4+T细胞的表型、滑膜调节性T细胞的功能、PB和SF中CD4+CD25-效应T细胞对调节性T细胞免疫调节特性的敏感性，并研究调节性T细胞对SF效应T细胞细胞因子分泌的抑制作用。
通过流式细胞术测定JIA患者和健康供体PB和SF中效应T细胞和调节性T细胞的表型。在3H-胸腺嘧啶核苷增殖试验中对分离的调节性T细胞和效应T细胞的功能进行定量。使用Bio-Plex Pro分析方法分析细胞因子水平。
与PB相比，SF中活化和分化的CD4+CD45RO+T细胞数量显著增加。SF效应T细胞对来自PB和SF的调节性T细胞抑制作用的敏感性受损，与CD69和HLA-DR的表达呈负相关。然而，SF效应T细胞的细胞因子分泌部分受到SF调节性T细胞的抑制。
我们的研究结果表明，JIA患者的SF中调节功能受损，表现为效应T细胞对功能性调节性T细胞免疫调节的抵抗。SF效应T细胞的这种抵抗可能归因于其活化的表型。
