Cameron P U, Forsum U, Teppler H, Granelli-Piperno A, Steinman R M
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Clin Exp Immunol. 1992 May;88(2):226-36. doi: 10.1111/j.1365-2249.1992.tb03066.x.
We have considered the possibility that antigen-presenting cells of the dendritic cell lineage may be infected in vivo and spread HIV-1 at the time dendritic cells initiate the clonal expansion of antigen-specific T cells. Dendritic cells were isolated from 25 HIV-1-infected subjects (CDC stages II-IV). Fewer dendritic cells were recovered from most infected subjects. Reduced numbers of total non-T cells were also found in these patients, so that preferential loss of dendritic cells did not occur. Dendritic cell function was assessed by stimulatory capacity for allogeneic CD4+ T cells in the mixed leucocyte reaction (MLR). Potent MLR stimulator activity was retained in the dendritic cell-enriched populations from HIV-infected patients. Seven out of nine patients without AIDS (asymptomatic, lymphadenopathy or ARC) and three out of six patients with AIDS had proliferative responses equivalent to those induced by dendritic cells from controls. Dendritic cells from HIV+ subjects were able to initiate the expansion of allogeneic CD4+ T cell clones with cloning efficiency not different from controls and without evidence of cytopathic effect in the expanding CD4+ clones. In situ hybridization of the different mononuclear cell populations with a gag-specific riboprobe demonstrated positive cells in the T cell fractions of 12 of the 15 patients tested. None of the asymptomatic or ARC patients had riboprobe-positive cells in the dendritic cell-enriched populations. Four out of nine patients with AIDS had cells positive for HIV-1 expression in the dendritic cell-enriched fraction. However, the positive cells had the nuclear profile of lymphocytes, and by cytofluorography some residual low-density T cells were present. By limiting dilution and polymerase chain reaction (PCR), CD4+ lymphocytes carried HIV provirus in inocula of 500-5000 cells, while provirus could only be detected in 50,000 cells from the dendritic cell-enriched fraction. The latter signal may be due to the demonstrated levels of T cell contamination. Our data indicate that productive or latent HIV-1 infection of blood dendritic cells in vivo is rare, certainly no greater than in T lymphocytes, and that in vitro dendritic cell preparations from patients can expand CD4+ T cells efficiently and therefore may be able to expand T cells with immunotherapeutic activity.
我们已经考虑过这样一种可能性，即在树突状细胞系的抗原呈递细胞可能在体内被感染，并在树突状细胞启动抗原特异性T细胞的克隆扩增时传播HIV-1。从25名HIV-1感染受试者（疾病控制中心II-IV期）中分离出树突状细胞。大多数感染受试者回收的树突状细胞较少。在这些患者中还发现总非T细胞数量减少，因此不存在树突状细胞的优先丢失。通过混合淋巴细胞反应（MLR）中对同种异体CD4+T细胞的刺激能力来评估树突状细胞功能。来自HIV感染患者的富含树突状细胞的群体保留了强大的MLR刺激活性。9名无艾滋病患者（无症状、淋巴结病或艾滋病相关综合征）中的7名以及6名艾滋病患者中的3名具有与对照树突状细胞诱导的增殖反应相当的反应。来自HIV+受试者的树突状细胞能够启动同种异体CD4+T细胞克隆的扩增，克隆效率与对照无异，并且在扩增的CD4+克隆中没有细胞病变效应的证据。用gag特异性核糖探针对不同单核细胞群体进行原位杂交，在15名受试患者中的T细胞部分显示出阳性细胞。无症状或艾滋病相关综合征患者的富含树突状细胞的群体中均没有核糖探针阳性细胞。9名艾滋病患者中有4名在富含树突状细胞的部分中有HIV-1表达阳性的细胞。然而，阳性细胞具有淋巴细胞的核形态，并且通过细胞荧光术发现存在一些残留的低密度T细胞。通过有限稀释和聚合酶链反应（PCR），在接种500-5000个细胞时，CD4+淋巴细胞携带HIV前病毒，而仅在富含树突状细胞部分的50000个细胞中才能检测到前病毒。后一个信号可能归因于已证实的T细胞污染水平。我们的数据表明，体内血液树突状细胞的HIV-1有效感染或潜伏感染很少见，肯定不高于T淋巴细胞，并且来自患者的体外树突状细胞制剂能够有效地扩增CD4+T细胞，因此可能能够扩增具有免疫治疗活性的T细胞。
