CD13+ CD4+ CD25hi regulatory T cells exhibit higher suppressive function and increase with tumor stage in non-small cell lung cancer patients
CD13+ CD4+ CD25hi regulatory T cells exhibit higher suppressive function and increase with tumor stage in non-small cell lung cancer patients
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DOI：
10.4161/cc.8.16.9302
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发表时间：
2009-08-15
期刊：
影响因子：
4.3
通讯作者：
Shu, Yongqian
中科院分区：
文献类型：
--
作者：
Ju, Songwen;Qiu, Hongxia;Shu, Yongqian
外周血中的调节性T细胞（Treg）和肿瘤浸润淋巴细胞（TIL）在抑制癌症患者的抗肿瘤免疫应答中起关键作用，并且与临床结果相关。我们在非小细胞肺癌（NSCLC）患者外周血中的CD 4（+）CD 25（hi）Treg细胞中鉴定了一个重要的亚群，即CD 13（+）CD 4（+）CD 25（hi）Treg细胞。从NSCLC患者（n = 72）或健康供体（n = 30）中分离外周血单核细胞（PBMC）。进行流式细胞术分析以研究CD 4（+）CD 25（hi）Treg细胞上的细胞表面或细胞内标志物的表达。通过与PHA激活的CD 4（+）CD 25（-）T细胞共培养来评价CD 13（+）CD 4（+）CD 25（hi）Treg细胞的免疫抑制功能。结果表明，与CD 4（+）CD 25（Low/-）T细胞相比，CD 13在CD 4（+）CD 25（hi）Treg细胞上表达明显富集。CD 13（+）CD 4（+）CD 25（hi）Treg细胞还表达更高水平的Foxp 3、CTLA-4、膜结合转化生长因子β 1（mTGF β 1）和B7-H1，并且更抑制CD 25表达和CD 4（+）CD 25（-）T细胞的增殖。另外，我们发现抗CD 13 mAb（WM 15）显著抑制CD 13（+）CD 4（+）CD 25（hi）Treg细胞上Foxp 3、CTLA-4、B7-H1、mTGF β 1的表达以及TGF β 1和IL-10的分泌，并且这些细胞抑制CD 25表达和CD 4（+）CD 25（-）T细胞增殖的能力也被WM 15抑制。有趣的是，在NSCLC中，CD 4（+）CD 25（hi）Treg群体中的CD 13（+）CD 4（+）CD 25（hi）Treg细胞的百分比显著增加，并且与病理分期相关：健康供体（9.84% +/- 2.23%）
Regulatory T cells (Tregs) in peripheral blood and tumor infiltrating lymphocytes (TILs) play crucial roles in suppressing anti-tumor immune responses in cancer patients, and correlate with clinical outcomes. We identified an important subpopulation, CD13(+)CD4(+)CD25(hi)Treg cells, among CD4(+)CD25(hi)Treg cells in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with NSCLC (n = 72) or from healthy donors (n = 30). Flow cytometric analyses were performed to study the expression of cell-surface or intracellular markers on the CD4(+)CD25(hi)Treg cells. The immune suppressive function of CD13(+)CD4(+)CD25(hi)Treg cells was evaluated by co-culturing with CD4(+)CD25(-)T cells that were activated by PHA. Our data showed that, compared with CD4(+)CD25(Low/-)T cells, CD13 expression was enriched on CD4(+)CD25(hi)Treg cells. The CD13(+)CD4(+)CD25(hi)Treg cells also expressed higher levels of Foxp3, CTLA-4, membrane-bound transforming growth factor beta 1 (mTGF beta 1) and B7-H1, and are more suppressive to CD25 expression and proliferation of CD4(+)CD25(-)T cells. Additionally, we showed that the expression of Foxp3, CTLA-4, B7-H1, mTGF beta 1 and the secretion of TGF beta 1 and IL-10 on CD13(+)CD4(+)CD25(hi)Treg cells was significantly suppressed by anti-CD13 mAb (WM15), and the ability of these cells to suppress CD25 expression and proliferation of CD4(+)CD25(-)T cells was inhibited by WM15 as well. Interestingly, the percentage of CD13(+)CD4(+)CD25(hi)Treg cells among the CD4(+)CD25(hi)Treg population increased significantly and correlated with pathological stage in NSCLC: healthy donor (9.84% +/- 2.23%)