Granelli-Piperno A, Delgado E, Finkel V, Paxton W, Steinman R M
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021, USA.
J Virol. 1998 Apr;72(4):2733-7. doi: 10.1128/JVI.72.4.2733-2737.1998.
Dendritic cells (DCs) can develop from CD14+ peripheral blood monocytes cultured in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). By 6 days in culture, the cells have the characteristics of immature DCs and can be further induced to mature by inflammatory stimuli or by monocyte-conditioned medium. After infection with macrophagetropic (M-tropic) human immunodeficiency virus type 1 (HIV-1), monocytes and mature DCs show a block in reverse transcription and only form early transcripts that can be amplified with primers for the R/U5 region. In contrast, immature DCs cultured for 6 or 11 days in GM-CSF and IL-4 complete reverse transcription and show a strong signal when LTR/gag primers are used. Blood monocytes and mature DCs do not replicate HIV-1, whereas immature DCs can be productively infected, but only with M-tropic HIV-1. The virus produced by immature DCs readily infects activated T cells. Although mature DCs do not produce virus, these cells transmit both M- and T-tropic virus to T cells. In the cocultures, both DCs and T cells must express functional chemokine coreceptors for viral replication to occur. Therefore, the developmental stage of DCs can influence the interaction of these cells with HIV-1 and influence the extent to which M-tropic and T-tropic virus can replicate.
树突状细胞(DCs)可由在粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)中培养的CD14 +外周血单核细胞发育而来。培养6天后,这些细胞具有未成熟DCs的特征,并且可通过炎性刺激或单核细胞条件培养基进一步诱导成熟。在用嗜巨噬细胞性1型人类免疫缺陷病毒(HIV-1)感染后,单核细胞和成熟DCs在逆转录过程中出现阻滞,仅形成可用R/U5区域引物扩增的早期转录本。相比之下,在GM-CSF和IL-4中培养6天或11天的未成熟DCs可完成逆转录,并且在用LTR/gag引物时显示出强信号。血液单核细胞和成熟DCs不复制HIV-1,而未成熟DCs可被有效感染,但仅被嗜巨噬细胞性HIV-1感染。未成熟DCs产生的病毒可轻易感染活化的T细胞。虽然成熟DCs不产生病毒,但这些细胞可将嗜巨噬细胞性和嗜T细胞性病毒传递给T细胞。在共培养中,DCs和T细胞都必须表达功能性趋化因子共受体才能发生病毒复制。因此,DCs的发育阶段可影响这些细胞与HIV-1的相互作用,并影响嗜巨噬细胞性和嗜T细胞性病毒的复制程度。