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浆细胞样树突状细胞(PDC)是人类淋巴结中天然产生细胞因子的主要树突状细胞亚群。

Plasmacytoid dendritic cells (PDC) are the major DC subset innately producing cytokines in human lymph nodes.

作者信息

Cox Karina, North Margaret, Burke Michael, Singhal Hemant, Renton Sophie, Aqel Nayef, Islam Sabita, Knight Stella C

机构信息

Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Northwick Park and St. Marks Campus, Harrow, Middlesex, United Kingdom.

出版信息

J Leukoc Biol. 2005 Nov;78(5):1142-52. doi: 10.1189/jlb.1103532.

DOI:10.1189/jlb.1103532
PMID:16260587
Abstract

Plasmacytoid dendritic cells (PDC) constitute a distinct subset of DC found in human peripheral lymph nodes (LN), but little is known about their function. Cell suspensions were prepared from tumor draining LN (n=20) and control LN (n=11) of women undergoing surgical resection for primary breast cancer and elective surgery for benign conditions, respectively. Using four-color flow cytometry, human leukocyte antigen-DR+ DC subsets were identified phenotypically. The proportions and numbers of cells innately producing interleukin (IL)-4, IL-10, IL-12, and interferon-gamma (IFN-gamma) were also measured from intracellular accumulation of cytokine after blocking with monensin. All flow cytometry data were collected without compensation and were compensated off-line using the Winlist algorithm (Verity software). This package also provided the subtraction program to calculate percentage positive cells and intensity of staining. PDC (CD11c-, CD123+) expressed more cytokines than did myeloid DC (CD11c+) or CD1a+ putative "migratory" DC (P<0.001). LN PDC from patients with a good prognosis (px; n=11) demonstrated a relative increase in IL-12 and IFN-gamma expression (median IL-10:IL-12 ratio=0.78 and median IL-4:IFN-gamma ratio=0.7), and PDC from LN draining poor px cancer (n=9) showed a relative increase in IL-10 and IL-4 expression (median IL-10:IL-12 ratio=1.31 and median IL-4:IFN-gamma ratio=2.6). The difference in IL-4:IFN-gamma expression between good and poor px cancer groups was significant (P<0.05). Thus, PDC innately producing cytokines were identified in cell suspensions from human LN, and the character of PDC cytokine secretion may differ between two breast cancer prognostic groups. We speculate that a shift towards PDC IL-10 and IL-4 expression could promote tumor tolerance in LN draining poor px breast cancer.

摘要

浆细胞样树突状细胞(PDC)是存在于人类外周淋巴结(LN)中的一种独特的树突状细胞亚群,但其功能鲜为人知。分别从接受原发性乳腺癌手术切除的女性的肿瘤引流淋巴结(n = 20)和接受良性疾病择期手术的女性的对照淋巴结(n = 11)中制备细胞悬液。使用四色流式细胞术,从表型上鉴定人白细胞抗原-DR +树突状细胞亚群。在用莫能菌素阻断后,还通过细胞内细胞因子积累来测量天然产生白细胞介素(IL)-4、IL-10、IL-12和干扰素-γ(IFN-γ)的细胞比例和数量。所有流式细胞术数据均在未进行补偿的情况下收集,并使用Winlist算法(Verity软件)进行离线补偿。该软件包还提供了减法程序来计算阳性细胞百分比和染色强度。PDC(CD11c-,CD123 +)比髓样树突状细胞(CD11c +)或CD1a +推定的“迁移性”树突状细胞表达更多的细胞因子(P <0.001)。预后良好(px;n = 11)患者的淋巴结PDC表现出IL-12和IFN-γ表达相对增加(IL-10:IL-12比值中位数= 0.78,IL-4:IFN-γ比值中位数= 0.7),而引流预后不良px癌症(n = 9)的淋巴结中的PDC表现出IL-10和IL-4表达相对增加(IL-10:IL-12比值中位数= 1.31,IL-4:IFN-γ比值中位数= 2.6)。预后良好和预后不良px癌症组之间IL-4:IFN-γ表达的差异具有统计学意义(P <0.05)。因此,在人淋巴结的细胞悬液中鉴定出了天然产生细胞因子的PDC,并且在两个乳腺癌预后组之间,PDC细胞因子分泌的特征可能有所不同。我们推测,向PDC的IL-10和IL-4表达转变可能会促进引流预后不良px乳腺癌的淋巴结中的肿瘤耐受性。

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