IL-10在B细胞非霍奇金淋巴瘤中诱导免疫抑制性CD14+HLA-DRlow/−单核细胞的发育
IL-10 induces the development of immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma
原文发布日期:2015-07-31
DOI: 10.1038/bcj.2015.56
类型: Original Article
开放获取: 是
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The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/− phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/− monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/− population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/− phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/− population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/− population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/− monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell NHL.
单核细胞和巨噬细胞在B细胞非霍奇金淋巴瘤(NHL)中的生物学作用尚未被完全阐明。我们既往研究发现,B细胞NHL患者体内的单核细胞呈现免疫抑制性的CD14+HLA-DRlow/−表型,且该表型与不良预后相关。然而,淋巴瘤环境中CD14+HLA-DRlow/−单核细胞的形成机制仍不明确。本研究发现在B细胞NHL患者血清中升高的白细胞介素(IL)-10可诱导CD14+HLA-DRlow/−细胞群体的形成。通过分析B细胞NHL患者的外周血样本,我们观察到具有HLA-DRlow/−表型的CD14+单核细胞绝对数量较健康对照组显著增高,且与国际预后指数评分呈正相关。淋巴瘤患者血清IL-10水平较对照组明显升高,并与外周血单核细胞计数增加相关。体外实验证实IL-10处理可显著降低单核细胞HLA-DR表达,并促进CD14+HLA-DRlow/−群体扩增。研究进一步发现淋巴瘤B细胞可分泌IL-10,且淋巴瘤细胞培养上清液能够增加CD14+HLA-DRlow/−群体比例。值得注意的是,IL-10诱导的CD14+HLA-DRlow/−单核细胞可抑制T细胞的活化和增殖。综上,这些结果表明血清IL-10水平升高促进了B细胞NHL中免疫抑制性CD14+HLA-DRlow/−单核细胞数量的增加。
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