Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis.
Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis.
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DOI：
10.1186/ar4567
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发表时间：
2014-05-22
影响因子：
4.9
通讯作者：
Louis-Plence P
中科院分区：
文献类型：
--
作者：
Asnagli H;Martire D;Belmonte N;Quentin J;Bastian H;Boucard-Jourdin M;Fall PB;Mausset-Bonnefont AL;Mantello-Moreau A;Rouquier S;Marchetti I;Jorgensen C;Foussat A;Louis-Plence P
调节性T（Treg）细胞在预防自身免疫性疾病中起着至关重要的作用，并且是开发旨在以抗原特异性方式抑制炎症的疗法的理想靶点。1型调节性T（Tr 1）细胞通过其产生高水平白细胞介素10（IL-10）的能力来定义，这有助于其在几种情况下抑制病理性免疫应答的能力。本研究的目的是评估II型胶原特异性Tr 1（Col-Treg）细胞在两种小鼠类风湿性关节炎（RA）模型中的治疗潜力。从胶原特异性TCR转基因小鼠中分离和扩增Col-Treg克隆。研究了它们的细胞因子分泌谱和表型特征。在胶原-抗体-和胶原-诱导的关节炎模型中过继转移后评估Col-Treg细胞的治疗潜力。还研究了Col-Treg克隆对效应T细胞增殖的体内抑制机制。Col-Treg克隆的特征在于其特异性细胞因子谱（IL-10高IL-4高IFN-γint），并介导非接触性免疫抑制。它们还与天然THP共享GITR、CD 39和颗粒酶B的高表达。单次输注Col-Treg细胞在预防和治疗环境中均降低了关节炎的发病率和临床症状，对II型胶原抗体具有显著影响。重要的是，注射抗原特异性Tr 1细胞显著降低了体内抗原特异性效应T细胞的增殖。我们的研究结果证明了Col-Treg细胞在两种RA模型中的治疗潜力，为Col-Treg可能成为目前治疗难治性RA患者的有效细胞疗法提供了证据。
Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for the development of therapies designed to suppress inflammation in an antigen-specific manner. Type 1 regulatory T (Tr1) cells are defined by their capacity to produce high levels of interleukin 10 (IL-10), which contributes to their ability to suppress pathological immune responses in several settings. The aim of this study was to evaluate the therapeutic potential of collagen type II–specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice. Col-Treg clones were isolated and expanded from collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibody– and collagen-induced arthritis models. The in vivo suppressive mechanism of Col-Treg clones on effector T-cell proliferation was also investigated. Col-Treg clones are characterized by their specific cytokine profile (IL-10highIL-4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and granzyme B. A single infusion of Col-Treg cells reduced the incidence and clinical symptoms of arthritis in both preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific Tr1 cells decreased the proliferation of antigen-specific effector T cells in vivo significantly. Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients whose disease is refractory to current treatments.
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影响因子：
5.6
作者：
Brun, Valerie;Bastian, Herve;Foussat, Arnaud
通讯作者：
Foussat, Arnaud
影响因子：
4.4
作者：
Broere, Femke;Wieten, Lotte;van Eden, Willem
通讯作者：
van Eden, Willem
影响因子：
14.8
作者：
Khachigian, Levon M.
通讯作者：
Khachigian, Levon M.
影响因子：
--
作者：
Joosten, LAB;Lubberts, E;vandenBerg, WB
通讯作者：
vandenBerg, WB
影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe