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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Critical roles for IFN-β in lymphoid development, myelopoiesis, and tumor development: Links to tumor necrosis factor α
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Critical roles for IFN-β in lymphoid development, myelopoiesis, and tumor development: Links to tumor necrosis factor α

机译：IFN-β在淋巴发育，骨髓生成和肿瘤发展中的关键作用：与肿瘤坏死因子α的联系

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摘要

We have generated mice null for IFN-β and report the diverse consequences of IFN-β for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-β~(-/-) mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor a production, relative to IFN-β~(+/+) mice. Notably, constitutive and induced expression of tumor necrosis factor a is reduced in the spleen and bone marrow (BM) macro-phages, respectively, of IFN-β~(-/-) mice. We also observe an altered splenic architecture in IFN-β~(-/-) mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-β~(-/-) mice, associated with a decrease in B220~(+ve/high)/CD43~(-ve) BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-β~(-/-) mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-β~(-/-) background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-β~(-/-) mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-β is required during different stages of maturation in the development of the immune system.
机译：我们已经产生了对IFN-β无效的小鼠，并报告了IFN-β对免疫的先天性和适应性的不同影响。尽管IFN-β〜（-/-）小鼠外周血，胸腺和脾脏中CD4和CD8 T细胞群的比例平衡没有异常，但活化的淋巴结和脾T淋巴细胞显示出增强的T细胞增殖和肿瘤减少相对于IFN-β〜（+ / +）小鼠，坏死因子a的产生。值得注意的是，在TNF-α-（-/-）小鼠的脾脏和骨髓（BM）巨噬细胞中，肿瘤坏死因子α的组成型和诱导表达分别降低。我们还观察到在IFN-β〜（-/-）小鼠中脾脏结构的改变和驻留巨噬细胞的减少。我们发现在IFN-β〜（-/-）小鼠中B细胞成熟的潜在缺陷，与B220〜（+ ve / high）/ CD43〜（-ve）BM来源的细胞减少和BP减少有关-1，IgM和CD23表达。在IFN-β〜（-/-）小鼠中，循环中的IgM-，Mac-1和Gr-1阳性细胞也大大减少。循环巨噬细胞和粒细胞数量的减少可能反映了小鼠原始BM造血功能的成熟缺陷，表现为集落形成单位粒细胞巨噬细胞减少。我们着手评估在IFN-β〜（-/-）背景下恶性细胞的体内生长，并提供证据表明Lewis肺癌特异性肿瘤在IFN-β〜（-/-）小鼠中更具侵略性。总而言之，我们的数据表明，除了对肿瘤细胞的直接生长抑制作用外，在免疫系统发育的不同成熟阶段还需要IFN-β。

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