Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study.

Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study.
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DOI:
10.1186/1471-2474-15-281
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发表时间:
2014-08-19
影响因子:
2.3
通讯作者:
Mikecz K
Mikecz K
中科院分区:
医学3区
文献类型:
--
作者:
Kurkó J;Vida A;Glant TT;Scanzello CR;Katz RS;Nair A;Szekanecz Z;Mikecz K

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骨髓源性抑制细胞(MDSC)是一种异质性先天免疫细胞群体,具有粒细胞样或单核细胞样表型,具有独特的抑制T细胞反应的能力。MDSC已被证明在癌症患者中积累,但最近的研究表明,这些细胞也存在于患有自身免疫性疾病的人类和动物中。我们先前在实验性自身免疫性关节炎小鼠的滑液(SF)中发现了MDSC。本研究的目的是鉴定类风湿关节炎(RA)患者SF中的MDSC。使用MDSC细胞表面标志物的抗体通过流式细胞术以及通过细胞形态学分析来研究RA SF细胞。离体测定RA SF细胞对自体外周血T细胞的抑制活性。我们采用抗原非特异性(抗CD 3/CD 28抗体)和抗原特异性(同种异体细胞)诱导系统来测试RA SF细胞对自体T细胞增殖的影响。RA患者的SF含有MDSC样细胞,其中大多数显示粒细胞(中性粒细胞)样表型和形态。RA SF细胞在共培养时显著抑制抗CD 3/CD 28刺激的自体T细胞的增殖。当并排比较时,RA SF细胞对同种异体抗原诱导的自体T细胞增殖的抑制作用比抗CD 3/CD 28诱导的自体T细胞增殖的抑制作用更深刻。MDSC存在于RA SF细胞中,其通常被认为是炎性中性粒细胞。我们的研究结果表明,SF中存在嗜中性粒细胞样MDSC可能是有益的,因为这些细胞能够限制RA中关节浸润T细胞的扩增。本文的在线版本(doi:10.1186/1471-2474-15-281)包含补充材料,可供授权用户使用。
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells with a granulocyte-like or monocyte-like phenotype and a unique ability to suppress T-cell responses. MDSCs have been shown to accumulate in cancer patients, but recent studies suggest that these cells are also present in humans and animals suffering from autoimmune diseases. We previously identified MDSCs in the synovial fluid (SF) of mice with experimental autoimmune arthritis. The goal of the present study was to identify MDSCs in the SF of patients with rheumatoid arthritis (RA). RA SF cells were studied by flow cytometry using antibodies to MDSC cell surface markers as well as by analysis of cell morphology. The suppressor activity of RA SF cells toward autologous peripheral blood T cells was determined ex vivo. We employed both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific (allogeneic cells) induction systems to test the effects of RA SF cells on the proliferation of autologous T cells. SF from RA patients contained MDSC-like cells, the majority of which showed granulocyte (neutrophil)-like phenotype and morphology. RA SF cells significantly suppressed the proliferation of anti-CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by side, RA SF cells had a more profound inhibitory effect on the alloantigen-induced than the anti-CD3/CD28-induced proliferation of autologous T cells. MDSCs are present among RA SF cells that are commonly regarded as inflammatory neutrophils. Our results suggest that the presence of neutrophil-like MDSCs in the SF is likely beneficial, as these cells have the ability to limit the expansion of joint-infiltrating T cells in RA. The online version of this article (doi:10.1186/1471-2474-15-281) contains supplementary material, which is available to authorized users.
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发表时间: 2011-07
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