Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis.
Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis.
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DOI：
10.1002/art.34494
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发表时间：
2012-10
影响因子：
--
通讯作者：
Mikecz, Katalin
中科院分区：
文献类型：
--
作者：
Egelston, Colt;Kurko, Julia;Besenyei, Timea;Tryniszewska, Beata;Rauch, Tibor A.;Glant, Tibor T.;Mikecz, Katalin
确定关节炎关节滑液（SF）中存在的髓样细胞（如粒细胞）是否对获得性免疫产生影响。具体来说，我们研究了SF细胞，收获从小鼠关节蛋白多糖（PG）诱导的关节炎（PGIA），树突状细胞（DC）的成熟和抗原特异性T细胞增殖的影响。我们通过流式细胞术监测DC与SF或来自PGIA小鼠的脾髓样细胞共培养后的DC成熟（MHC II类和CD 86表达）。使用从PG特异性T细胞受体转基因（PG-TCR-Tg）小鼠纯化的T细胞研究这些骨髓细胞对T细胞增殖的影响。骨髓细胞的表型分析采用免疫染色，RT-PCR，蛋白质印迹，和生化测定。炎性SF细胞在共培养时显著抑制DC的成熟。与抗原负载的DC一起培养的PG-TCR-Tg T细胞在SF细胞的存在下显示出增殖的显著降低。来自关节炎小鼠的脾髓样细胞没有抑制作用。SF细胞不能抑制CD 3/CD 28刺激的相同T细胞的增殖，表明DC依赖性机制。SF细胞表现出髓源性抑制细胞（MDSC）的所有特征，并主要通过粒细胞样细胞产生一氧化氮和活性氧来发挥抑制作用。PGIA小鼠关节中的SF含有粒细胞MDSC群，其有效抑制DC成熟和T细胞增殖。这些MDSC有可能限制自身反应性T细胞的扩增，从而打破自身免疫和炎症的恶性循环。
To determine whether myeloid cells (such as granulocytes) present in the synovial fluid (SF) of arthritic joints have an impact on adaptive immunity. Specifically, we investigated the effects of SF cells, harvested from the joints of mice with proteoglycan (PG)-induced arthritis (PGIA), on dendritic cell (DC) maturation and antigen-specific T-cell proliferation. We monitored DC maturation (MHC class II and CD86 expression) by flow cytometry upon co-culture of DCs with SF or spleen myeloid cells from mice with PGIA. The effects of these myeloid cells on T-cell proliferation were studied using T cells purified from PG-specific T cell receptor transgenic (PG-TCR-Tg) mice. Phenotypic analysis of myeloid cells was performed employing immunostaining, RT-PCR, Western blot, and biochemical assays. Inflammatory SF cells significantly suppressed the maturation of DCs upon co-culture. PG-TCR-Tg T cells cultured with antigen-loaded DCs showed dramatic decreases in proliferation in the presence of SF cells. Spleen myeloid cells from arthritic mice did not have suppressive effects. SF cells were unable to suppress CD3/CD28-stimulated proliferation of the same T cells, suggesting a DC-dependent mechanism. SF cells exhibited all of the characteristics of myeloid-derived suppressor cells (MDSCs), and exerted suppression primarily through production of nitric oxide and reactive oxygen species by granulocyte-like cells. SF in the joints of mice with PGIA contains a population of granulocytic MDSCs that potently suppress DC maturation and T-cell proliferation. These MDSCs have the potential to limit the expansion of autoreactive T cells, thus breaking the vicious cycle of autoimmunity and inflammation.
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影响因子：
4.3
作者：
Bansal, Savita;Siddarth, Manushi;Tripathi, Ashok K.
通讯作者：
Tripathi, Ashok K.
影响因子：
--
作者：
Berlo, Suzanne E.;Guichelaar, Teun;Glant, Tibor T.
通讯作者：
Glant, Tibor T.
影响因子：
4.4
作者：
Bennouna, S;Bliss, SK;Denkers, EY
通讯作者：
Denkers, EY
影响因子：
4
作者：
Belz, GT;Heath, WR;Carbone, FR
通讯作者：
Carbone, FR
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G