PHENOTYPICAL AND FUNCTIONAL-CHARACTERIZATION OF FC-GAMMA RECEPTOR-I (CD64)-NEGATIVE MONOCYTES, A MINOR HUMAN MONOCYTE SUBPOPULATION WITH HIGH ACCESSORY AND ANTIVIRAL ACTIVITY
PHENOTYPICAL AND FUNCTIONAL-CHARACTERIZATION OF FC-GAMMA RECEPTOR-I (CD64)-NEGATIVE MONOCYTES, A MINOR HUMAN MONOCYTE SUBPOPULATION WITH HIGH ACCESSORY AND ANTIVIRAL ACTIVITY
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DOI：
10.1002/eji.1830231213
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发表时间：
1993-12-01
影响因子：
5.4
通讯作者：
ERNST, M
中科院分区：
文献类型：
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作者：
GRAGEGRIEBENOW, E;LORENZEN, D;ERNST, M
Fc γ受体I阳性（CD 64+）和Fc γ受体I阴性（CD 64-）单核细胞制备高度纯化（淘析衍生）的人单核细胞通过细胞荧光细胞分选，并证明分离的CD 64+和CD 64单核细胞亚群的表型和功能分离。表面分析表明，CD 64+单核细胞的表面抗原模式对应于典型的未分离的单核细胞的表型。相比之下，CD 64-单核细胞的特征在于主要组织相容性复合体（MHC）I类抗原（HLA-A、-B、-C）和MHC II类抗原（HLA-DR、-DP、-DQ）的高表达，以及单核细胞特异性标志物CD 14的低表达，所述标志物CD 14在几乎所有CD 64+单核细胞上发现。然而，75%的CD 64-细胞被发现是酯酶阳性，85%的单核细胞/巨噬细胞特异性细胞内抗原CD 68阳性。此外，CD 64-单核细胞显示出比CD 64+单核细胞显著更高的CD 45 RA和Fc γ受体III（CD 16）表达，但缺乏自然杀伤细胞标志物CD 56和CD 57。功能研究表明，在抗原驱动的T细胞活化中，次要CD 64-单核细胞亚群的细胞比CD 64+单核细胞具有更高的辅助细胞能力。用PPD（结核菌素的纯化蛋白衍生物）预处理的CD 64-单核细胞比PPD预处理的CD 64+单核细胞诱导多达10倍的干扰素-γ，并且在应答的自体T细胞中也诱导更高的增殖。在混合白细胞反应中，T细胞也获得了类似的结果。干扰素-γ的释放和同种异体淋巴细胞的增殖始终高于照射的CD 64-单核细胞比照射的CD 64+单核细胞的存在。此外，当用纽卡斯尔病病毒刺激CD 64-和CD 64+单核细胞时，我们测量到CD 64-单核细胞比CD 64+单核细胞释放的干扰素-α高67倍，表明该亚群具有更高的抗病毒能力。CD 64-单核细胞显示出较低的活性，在吞噬unopsonized颗粒，也较低的酵母聚糖或乳胶诱导的化学发光比CD 64+单核细胞。这些发现表明，CD 64-单核细胞，虽然只占所有外周血单核细胞的不到10%，代表了一个单核细胞亚群有效地在体外与T细胞相互作用，此外，是α-干扰素的主要来源。
Fcgamma receptor I-positive (CD64+) and Fcgamma receptor I-negative (CD64-) monocytes were prepared from highly purified (elutriation-derived) human monocytes by cytofluorograph cell sorting, and a phenotypical and functional dissociation of the isolated CD64+ and CD64 monocyte subsets is demonstrated. Surface analyses revealed that the surface antigen pattern of CD64+ monocytes corresponds to the phenotype of typical unseparated monocytes. In contrast, CD64- monocytes are characterized by high expression of major histocompatibility complex (MHC) class I antigens (HLA-A, -B, -C) and MHC class II antigens (HLA-DR, -DP, -DQ), and low expression of the monocyte-specific marker CD14 which is found on nearly all CD64+ monocytes. However, 75% of the CD64- cells were found to be esterase-positive, and 85% were positive for the monocyte/macrophage-specific intracellular antigen CD68. Furthermore, CD64- monocytes show significantly higher expression of CD45RA and Fcgamma receptor III (CD 16) than CD64+ monocytes, but lack the natural killer cell markers CD56 and CD57. Functional studies showed that cells of the minor CD64- monocyte subset have a higher accessory cell capacity in antigen-driven T cell activation than CD64+ monocytes. CD64- monocytes pretreated with PPD (purified protein derivative of tuberculin) induced up to tentimes more-interferon-gamma and also higher proliferation in responding autologous T cells than PPD-pretreated CD64+ monocytes. Similar results were obtained for T cells in mixed leukocyte reaction. Interferon-gamma release and proliferation of allogeneic lymphocytes were consistently higher in the presence of irradiated CD64- monocytes than of irradiated CD64+ monocytes. Furthermore, when CD64- and CD64+ monocytes were stimulated with Newcastle disease virus, we measured an up to 67-fold higher interferon-alpha release from CD64- than from CD64+ monocytes, indicating a higher anti-viral capacity of this subset. CD64- monocytes showed lower activity in the phagocytosis of unopsonized particles and also lower zymosan- or latex-induced chemiluminescence than CD64+ monocytes. These findings indicate that CD64- monocytes, although comprising only less than 10% of all peripheral blood monocytes, represent a monocyte subpopulation efficiently interacting in vitro with T cells and, additionally, are the major source of interferon-alpha.