Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-β
Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-β
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DOI：
10.1189/jlb.0204090
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发表时间：
2004-09-01
影响因子：
5.5
通讯作者：
Sentman, CL
中科院分区：
文献类型：
--
作者：
Eriksson, M;Meadows, SK;Sentman, CL
自然杀伤（NK）细胞是人子宫内膜（EM）淋巴细胞的主要群体，NK细胞可以是改变局部免疫反应的细胞因子的重要来源。本研究的目的是确定NK细胞受体的原位表达，并测试子宫NK （uNK）细胞是否产生细胞因子，以及这种活性如何通过转化生长因子- β (tgf - β)调节。我们通过共聚焦显微镜观察到，人uNK细胞原位为CD56（+）、CD3（-）、CD57（-）、CD9（+）、CD94（+）、杀伤抑制受体（+）和CD16（+/-）。我们检测了来源于人EM的uNK细胞和uNK细胞克隆产生的细胞因子。用白细胞介素(IL)-12和IL-15刺激uNK细胞（两者都在人EM中表达），诱导干扰素- γ (ifn - γ)和IL-10的产生。tgf - β 1完全抑制uNK细胞克隆产生ifn - γ，呈剂量依赖性，抑制浓度50%值为20 pg/ml。同样浓度的tgf - β 1也能抑制uNK细胞克隆分泌IL-10。此外，在新鲜人子宫内膜细胞培养物中阻断内源性tgf - β增加了uNK细胞产生ifn - γ。这些数据表明，NK细胞具有独特的表型，不同于血液NK细胞。此外，数据表明，uNK细胞可以产生免疫调节细胞因子，并且局部产生的tgf - β 1对uNK细胞的抑制可能是调节人类EM中NK细胞功能的机制。
Natural killer (NK) cells are a major population of lymphocytes in the human endometrium (EM), and NK cells can be a significant source of cytokines that alter local immune responses. The aim of this study was to determine the expression of NK cell receptors in situ and to test whether uterine NK (uNK) cells produce cytokines and how this activity may be regulated by transforming growth factor-beta (TGF-beta). We observed that human uNK cells were CD56(+), CD3(-), CD57(-), CD9(+), CD94(+), killer inhibitory receptor(+), and CD16(+/-) in situ by confocal microscopy. We examined cytokine production by uNK cells and uNK cell clones derived from human EM. Stimulation of uNK cells with interleukin (IL)-12 and IL-15, both of which are expressed in the human EM, induced interferon-gamma (IFN-gamma) and IL-10 production. IFN-gamma production by uNK cell clones was completely inhibited by TGF-beta1 in a dose-dependent manner with an inhibitory concentration 50% value of 20 pg/ml. IL-10 secretion by uNK cell clones was also inhibited by TGF-beta1 at similar concentrations. Furthermore, blocking endogenous TGF-beta in fresh human endometrial cell cultures increased the production of IFN-gamma by uNK cells. These data indicate that uNK cells have a unique phenotype that is distinct from blood NK cells. Further, data demonstrate that uNK cells can produce immunoregulatory cytokines and that inhibition of uNK cells by locally produced TGF-beta1 is a likely mechanism to regulate NK cell function in the human EM.