Blauvelt A, Asada H, Saville M W, Klaus-Kovtun V, Altman D J, Yarchoan R, Katz S I
Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, USA.
J Clin Invest. 1997 Oct 15;100(8):2043-53. doi: 10.1172/JCI119737.
There is substantial evidence that dendritic cells (DC) residing within epithelial surfaces (e.g., Langerhans cells) are the initial cells infected with HIV after mucosal exposure to virus. To study DC-HIV interactions in detail, we propagated Langerhans cell-like DC from cord blood CD34(+) cells and from adult blood plastic-adherent PBMC in the presence of cytokines (GM-CSF, IL-4, and/or TNF-alpha). DC pulsed overnight with HIVBaL or HIVIIIB were infected productively with both viral subtypes (as assessed by PCR, supernatant p24 protein levels, electron microscopy, and antibody staining). Productive infection could be blocked by anti-CD4 mAbs, RANTES (regulated upon activation, normal T cell expressed and secreted) (for HIVBaL), stromal cell-derived factor-1 (for HIVIIIB), or azidothymidine added during the HIV pulse, as well as by blocking DC proliferation. However, pulsing DC with HIV under these blocking conditions had no effect on the ability of DC to capture virus and transmit infection to cocultured antigen-stimulated CD4(+) T cells. Thus, we show by several criteria that (a) productive infection of DC and (b) the ability of DC to capture virus are mediated through separate pathways. We suggest that strategies designed to block mucosal transmission of HIV should consider interfering with both virus infection and virus capture by DC.
有大量证据表明，位于上皮表面的树突状细胞（DC）（如朗格汉斯细胞）是黏膜接触病毒后最初感染HIV的细胞。为了详细研究DC与HIV的相互作用，我们在细胞因子（GM-CSF、IL-4和/或TNF-α）存在的情况下，从脐血CD34(+)细胞和成人血液塑料贴壁PBMC中培养出朗格汉斯细胞样DC。用HIVBaL或HIVIIIB过夜脉冲处理的DC被这两种病毒亚型有效感染（通过PCR、上清液p24蛋白水平、电子显微镜和抗体染色评估）。在HIV脉冲期间添加抗CD4单克隆抗体、RANTES（受激活调节，正常T细胞表达和分泌）（针对HIVBaL）、基质细胞衍生因子-1（针对HIVIIIB）或叠氮胸苷，以及阻断DC增殖，均可阻断有效感染。然而，在这些阻断条件下用HIV脉冲处理DC对DC捕获病毒并将感染传递给共培养的抗原刺激的CD4(+) T细胞的能力没有影响。因此，我们通过多项标准表明：（a）DC的有效感染和（b）DC捕获病毒的能力是通过不同途径介导的。我们建议，旨在阻断HIV黏膜传播的策略应考虑干扰病毒感染和DC对病毒的捕获。
