The susceptibility to X4 and R5 human immunodeficiency virus-1 strains of dendritic cells derived in vitro from CD34+ hematopoietic progenitor cells is primarily determined by their maturation stage
The susceptibility to X4 and R5 human immunodeficiency virus-1 strains of dendritic cells derived in vitro from CD34+ hematopoietic progenitor cells is primarily determined by their maturation stage
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DOI：
10.1182/blood.v93.11.3866.411k43_3866_3875
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发表时间：
1999-06-01
期刊：
影响因子：
20.3
通讯作者：
Gluckman, JC
中科院分区：
文献类型：
--
作者：
Canque, B;Bakri, Y;Gluckman, JC
树突状细胞（DC）于第8天从具有干细胞因子/Flt-3配体/粒细胞-巨噬细胞集落刺激因子(GM-CSF)/肿瘤坏死因子- α (tnf - α)/白细胞介素-4 （IL-4）的CD34（+）细胞培养物中分选。将未成熟的CCR5(+)CXCR4（低/-）DC暴露于CCR5依赖性人类免疫缺陷病毒(HIV)-1（Ba-L）导致生产性和细胞病变感染，而仅在CXCR4依赖性HIV-1（LAI）暴露的DC中发生低病毒生产。感染后48小时DC的PCR分析显示HIV-1（Ba-L）有效进入，但HIV-1（LAI）无效。CD40配体或单核细胞条件培养基诱导的HIV-1（Ba-L）感染DC的成熟使病毒产量减少约1 Log，而细胞变成CCR5（-）。然而，暴露于HIV-1（Ba-L）的成熟DC携带的病毒DNA比未成熟DC多15倍，排除了抑制病毒进入的可能性。同时，成熟DC中CXCR4的上调与HIV-1（LAI）的高效进入相一致，尽管如此，成熟DC中HIV-1（LAI）的复制水平与未成熟DC中相同。与这些发现一致，在AZT存在的情况下，HIV-1（Ba-L）感染的未成熟DC与CD3单克隆抗体激活的自体CD4(+) T淋巴细胞共培养可减少DC的病毒产生。最后，无论它们是来自CD1a(+)CD14（-）还是CD1a(-)CD14（+）前体，DC对HIV的容纳性没有差异，尽管CD1a(+)CD14（-）前体衍生的未成熟DC比CD1a(-)CD14（+）前体产生更高的HIV-1（Ba-L）量。因此，DC对HIV病毒的许可性和支持复制的能力主要取决于它们的成熟阶段。(C) 1999年由美国血液病学会出版。
Dendritic cells (DC) were sorted on day 8 from cultures of CD34(+) cells with stem cell factor/Flt-3 ligand/granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor-alpha (TNF-alpha)/interleukin-4 (IL-4). Exposing immature CCR5(+)CXCR4(lo/-) DC to CCR5-dependent human immunodeficiency virus (HIV)-1(Ba-L) led to productive and cytopathic infection, whereas only low virus production occurred in CXCR4-dependent HIV-1(LAI)-exposed DC. PCR analysis of the DC 48 hours postinfection showed efficient entry of HIV-1(Ba-L) but not of HIV-1(LAI). CD40 ligand- or monocyte-conditioned medium-induced maturation of HIV-1(Ba-L)-infected DC reduced virus production by about 1 Log, while cells became CCR5(-). However, HIV-1(Ba-L)-exposed mature DC harbored 15-fold more viral DNA than their immature counterparts, ruling out inhibition of virus entry. Simultaneously, CXCR4 upregulation by mature DC coincided with highly efficient entry of HIV-1(LAI) which, nonetheless, replicated at the same low level in mature as in immature DC. In line with these findings, coculture of HIV-1(Ba-L)-infected immature DC with CD3 monoclonal antibody-activated autologous CD4(+) T lymphocytes in the presence of AZT decreased virus production by the DC. Finally, whether they originated from CD1a(+)CD14(-) or CD1a(-)CD14(+) precursors, DC did not differ as regards permissivity to HIV, although CD1a(+)CD14(-) precursor-derived immature DC could produce higher HIV-1(Ba-L) amounts than their CD1a(-)CD14(+) counterparts. Thus, both DC permissivity to, and capacity to support replication of, HIV is primarily determined by their maturation stage. (C) 1999 by The American Society of Hematology.