Yuan X-K, Zhao X-K, Xia Y-C, Zhu X, Xiao P
Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Int Med Res. 2011;39(4):1381-91. doi: 10.1177/147323001103900424.
This study investigated CD14(+)HLA-DR(-/low) cells in peripheral blood mononuclear cells (PBMCs) from 64 patients with bladder carcinoma (BC) and 14 healthy controls. Cell phenotypes were determined and CD14(+)HLA-DR(-/low) cells, CD14(+)HLA-DR(+) cells and PBMCs depleted of CD14(+)HLA-DR(-/low) cells were isolated. Proliferation of stimulated PBMCs and interferon-γ (IFN-γ) production after addition of CD14(+)HLA-DR(-/low) and CD14(+)HLA-DR(+) cells at different ratios were measured. IFN-γ production was also measured after addition of L-arginine and/or antitransforming growth factor-β (TGF-β) neutralizing monoclonal antibody, and in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The proportion of CD14(+)HLA-DR(-/low) cells in BC patients was significantly higher than in controls. CD14(+)HLA-DR(-/low) cells significantly decreased T-cell proliferation and IFN-γ production in a dose-dependent manner. This suppressive activity was partially reversed by L-arginine or anti-TGF-β. Enhanced IFN-γ secretion was also seen in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The level of CD14(+)HLA-DR(-/low) cells was associated with gender, tumour size, number of tumours, cancer pathological grade and clinical stage. CD14(+)HLA-DR(-/low) cells may represent a subpopulation of myeloid-derived suppressor cells in BC patients.
本研究调查了64例膀胱癌（BC）患者和14名健康对照者外周血单个核细胞（PBMC）中CD14(+)HLA-DR(-/低)细胞。测定细胞表型，并分离出CD14(+)HLA-DR(-/低)细胞、CD14(+)HLA-DR(+)细胞以及去除CD14(+)HLA-DR(-/低)细胞的PBMC。测量了以不同比例添加CD14(+)HLA-DR(-/低)细胞和CD14(+)HLA-DR(+)细胞后刺激的PBMC的增殖情况以及干扰素-γ（IFN-γ）的产生。在添加L-精氨酸和/或抗转化生长因子-β（TGF-β）中和单克隆抗体后，以及在去除CD14(+)HLA-DR(-/低)细胞的PBMC中，也测量了IFN-γ的产生。BC患者中CD14(+)HLA-DR(-/低)细胞的比例显著高于对照组。CD14(+)HLA-DR(-/低)细胞以剂量依赖的方式显著降低T细胞增殖和IFN-γ的产生。L-精氨酸或抗TGF-β可部分逆转这种抑制活性。在去除CD14(+)HLA-DR(-/低)细胞的PBMC中也观察到IFN-γ分泌增强。CD14(+)HLA-DR(-/低)细胞的水平与性别、肿瘤大小、肿瘤数量、癌症病理分级和临床分期相关。CD14(+)HLA-DR(-/低)细胞可能代表BC患者中髓系来源抑制细胞的一个亚群。
