Keenihan Sarah N Hudson, Robertson Sarah A
Department of Obstetrics and Gynaecology and Reproductive Medicine Unit, Adelaide University, Adelaide, South Australia, 5005, Australia.
Biol Reprod. 2004 Jun;70(6):1562-72. doi: 10.1095/biolreprod.103.024794. Epub 2004 Feb 6.
The dendritic cells and related antigen-presenting cells (APCs) that activate lymphocytes for acquired immunity in the female reproductive tract are not well characterized. The aim of the present study was to examine heterogeneity among uterine APCs in mice and, specifically, to determine whether phenotypically and functionally distinct subpopulations of dendritic cells and macrophages can be identified. Using immunohistochemistry, abundant cells expressing APC-restricted molecules major histocompatibility complex (MHC) class II, F4/80, class A scavenger receptor, macrosialin, and sialoadhesin were evident in estrous mice. Cells expressing the costimulatory molecule B7-2 were rarely observed. Flow cytometric analysis revealed three subpopulations of uterine APCs. Undifferentiated macrophages were F4/80-positive (+), MHC class II-negative (-) cells, of which 70-80% expressed CD11b, but few expressed class A scavenger receptor, macrosialin, or sialoadhesin. Mature macrophages were F4/80+/MHC class II+ cells, of which approximately 50% expressed CD11b, class A scavenger receptor, macrosialin, and sialoadhesin. Uterine dendritic cells were F4/ 80-/MHC class II+ cells, with stimulatory immunoaccessory function relative to uterine macrophages and heterogeneous expression of dendritic markers 33D1, DEC205, CD11c, and CD1. Experiments in ovariectomized mice showed that undifferentiated macrophages were steroid hormone dependent but that mature macrophages and dendritic cells persisted after depletion of ovarian steroid hormones, although with altered phenotypes. In summary, our findings identify three discrete populations of APCs inhabiting the murine uterus and suggest that both mature macrophages and dendritic cells differentiate from undifferentiated macrophage precursor cells. Plasticity in the ontogenetic and functional relationships between uterine dendritic cells and macrophages likely is critical in regulating immune responses conducive to reproductive success.
在雌性生殖道中激活淋巴细胞以实现获得性免疫的树突状细胞及相关抗原呈递细胞（APC）尚未得到充分表征。本研究的目的是检测小鼠子宫APC的异质性，具体而言，确定是否能够识别出在表型和功能上不同的树突状细胞和巨噬细胞亚群。利用免疫组织化学方法，在发情期小鼠中明显可见大量表达APC限制性分子主要组织相容性复合体（MHC）II类、F4/80、A类清道夫受体、巨唾液酸蛋白和唾液粘附素的细胞。很少观察到表达共刺激分子B7-2的细胞。流式细胞术分析揭示了子宫APC的三个亚群。未分化的巨噬细胞是F4/80阳性（+）、MHC II类阴性（-）细胞，其中70-80%表达CD11b，但很少表达A类清道夫受体、巨唾液酸蛋白或唾液粘附素。成熟巨噬细胞是F4/80+/MHC II+细胞，其中约50%表达CD11b、A类清道夫受体、巨唾液酸蛋白和唾液粘附素。子宫树突状细胞是F4/80-/MHC II+细胞，相对于子宫巨噬细胞具有刺激免疫辅助功能，并且树突状标记33D1、DEC205、CD11c和CD1表达不均一。对去卵巢小鼠的实验表明，未分化的巨噬细胞依赖类固醇激素，但成熟巨噬细胞和树突状细胞在卵巢类固醇激素耗竭后仍持续存在，尽管其表型发生了改变。总之，我们的研究结果确定了定居于小鼠子宫的三个离散的APC群体，并表明成熟巨噬细胞和树突状细胞均从未分化的巨噬细胞前体细胞分化而来。子宫树突状细胞和巨噬细胞之间个体发生及功能关系的可塑性可能对调节有利于生殖成功的免疫反应至关重要。
