Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host
Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host
复制标题
DOI：
10.1158/0008-5472.can-05-1299
复制
发表时间：
2006-01-15
期刊：
影响因子：
11.2
通讯作者：
Chen, SH
中科院分区：
文献类型：
--
作者：
Huang, B;Pan, PY;Chen, SH
骨髓抑制细胞（MSC）的积累与荷瘤小鼠和癌症患者的免疫抑制有关。MSC的抑制活性与骨髓标志物Gr-1、CD 115（巨噬细胞集落刺激因子受体）和F4/80的表达相关。Gr-1（+）CD 115（+）MSC除了能够在体外抑制T细胞增殖外，还可以在体内诱导Foxp 3（+）T调节细胞（Treg）的发育，其是无反应性和抑制性的。此外，Gr（.）1（+）CD 115（+）MSC在IFN-γ刺激下分别被诱导和增强。Treg的发展需要肿瘤特异性T细胞的抗原相关活化，依赖于IFN-γ和IL-10的存在，并且不依赖于MSC的一氧化氮介导的抑制机制。我们的数据为Gr-1（+）CD 115（+）MSC的表达提供了证据。介导Treg在荷瘤小鼠中的发展，并显示出一种新的免疫抑制机制，MSC可以通过该机制抑制抗肿瘤反应。
The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1(+)CD115(+) MSCs, in addition to being able to suppress T-cell proliferation in vitro, can induce the development of Foxp3(+) T regulatory cells (Treg) in vivo, which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-beta by Gr(..)1(+)CD115(+) MSCs was induced and enhanced, respectively, on IFN-gamma stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-gamma and IL-10, and is independent of the nitric oxide-mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1(+)CD115(+) MSC car.. mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses.