Perales M A, Skolnik P R, Lieberman J
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02155, USA.
AIDS Res Hum Retroviruses. 1996 May 20;12(8):659-68. doi: 10.1089/aid.1996.12.659.
CD8-depleted PBMCs from 20 HIV-1-seropositive donors were incubated in the presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2 or rIL-12 in five of seven asymptomatic subjects and was not induced by either cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced increased p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only in cell lines from 5 symptomatic subjects and then only marginally. In IL-2 containing cultures from subjects with minor symptoms of HIV infection, the mean p24 Ag was 320 +/- 217 pg/ml versus 27 +/- 6 in IL-12-containing cultures (p = 0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold compared to cultures from this group incubated with only rIL-2 (p = 0.03). Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from subjects who had had a major AIDS infection, although the number of CD4 cells in four of six of those cultures was markedly reduced. IL-4, IFN-gamma, and IL-10 production induced by exposure to IL-2 and/or IL-12 were also measured. In CD8-depleted cultures from all infected asymptomatic donors and from some symptomatic donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-gamma and IL-10 production. Cytokine-induced production of IL-4, IFN-gamma, and IL-10 was greater in cultures from asymptomatic donors than in cultures from symptomatic subjects. Our results suggest that IL-12 immunotherapy may be complicated by enhancement of viral expression in asymptomatic individuals.
来自20名HIV-1血清反应阳性供体的CD8缺失外周血单核细胞（PBMCs）在无细胞因子、重组白细胞介素-2（rIL-2）、重组白细胞介素-12（rIL-12）或两者存在的情况下进行培养。通过培养上清液中的p24抗原测量HIV-1复制，在7名无症状受试者中的5名中，rIL-2或rIL-12均可使HIV-1复制增加到相当程度，而在其余2名无症状受试者中，两种细胞因子均未诱导HIV-1复制。重组白细胞介素-2可使13名有症状受试者中的8名培养物中的p24增加，但rIL-12仅在5名有症状受试者的细胞系中诱导p24增加，且增加幅度很小。在感染HIV且有轻微症状的受试者的含白细胞介素-2培养物中，p24抗原的平均水平为320±217 pg/ml，而在含白细胞介素-12的培养物中为27±6 pg/ml（p = 0.03）。当rIL-12与rIL-2一起添加时，与仅用rIL-2培养的该组培养物相比，p24抗原水平降低了四倍（p = 0.03）。两种细胞因子对来自患有严重艾滋病感染的受试者的CD8缺失PBMCs中的病毒复制均无太大影响，尽管其中6份培养物中的4份中的CD4细胞数量明显减少。还测量了暴露于IL-2和/或IL-12诱导的IL-4、干扰素-γ（IFN-γ）和IL-10的产生。在来自所有感染无症状供体和一些有症状供体的CD8缺失培养物中，向rIL-2中添加rIL-12可降低IL-4并增加IFN-γ和IL-10的产生。无症状供体培养物中细胞因子诱导的IL-4、IFN-γ和IL-10的产生高于有症状受试者的培养物。我们的结果表明，IL-12免疫疗法可能会因无症状个体中病毒表达的增强而变得复杂。
