Li Geling, Hangoc Giao, Broxmeyer Hal E
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Biochem Biophys Res Commun. 2004 Sep 17;322(2):637-43. doi: 10.1016/j.bbrc.2004.07.172.
Peripheral blood CD14(+)CD16(++) monocytes (Mo) are a rare Mo subpopulation known to undergo expansion in various diseases. We show here that IL-10 in the presence of M-CSF and IL-4 triggers the generation of CD14(+)CD16(++) cells from highly purified human cord blood (CB) and adult blood Mo. CB Mo were more sensitive to this cytokine combination than adult Mo. IL-10-induced CD14(+)CD16(++) cells that expressed dendritic cell markers: CD80, CD86, HLA-DR, and CD83 and initiated significantly decreased allogeneic mixed lymphocyte reactions (MLRs). Blockage of CD86, but not CD80, further down-modulated MLRs induced by CD14(+)CD16(++)cells. CD14(+)CD16(++) cells had similar features to CD14(+)CD16(++) Mo in that they expressed increased level of CCR5, efficiently produced TNF-alpha, and displayed higher MLR than CD14(+)CD16(-) Mo. Together, these results demonstrate that M-CSF, IL-4, and IL-10 drive Mo into CD14(+)CD16(++) cells similar to those identified in vivo, and CB Mo, due to their increased responsiveness, may be a useful starting cell source to study differentiation of CD14(+)CD16(++) cells.
外周血CD14(+)CD16(++)单核细胞(Mo)是一种罕见的Mo亚群,已知在多种疾病中会发生扩增。我们在此表明,在M-CSF和IL-4存在的情况下,IL-10可促使高度纯化的人脐血(CB)和成人血Mo生成CD14(+)CD16(++)细胞。CB Mo对这种细胞因子组合比成人Mo更敏感。IL-10诱导的CD14(+)CD16(++)细胞表达树突状细胞标志物:CD80、CD86、HLA-DR和CD83,并显著降低异体混合淋巴细胞反应(MLR)。阻断CD86而非CD80可进一步下调CD14(+)CD16(++)细胞诱导的MLR。CD14(+)CD16(++)细胞与CD14(+)CD16(++) Mo具有相似特征,即它们表达的CCR5水平升高,能有效产生TNF-α,并且与CD14(+)CD16(-) Mo相比,显示出更高的MLR。总之,这些结果表明,M-CSF、IL-4和IL-10可促使Mo分化为与体内鉴定的细胞相似的CD14(+)CD16(++)细胞,并且CB Mo由于其反应性增强,可能是研究CD14(+)CD16(++)细胞分化的有用起始细胞来源。