Mikovits J A, Taub D D, Turcovski-Corrales S M, Ruscetti F W
Intramural Research Support Program, SAIC-Frederick, and the Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
J Virol. 1998 Jun;72(6):5231-8. doi: 10.1128/JVI.72.6.5231-5238.1998.
Studies on the development and function of CD4+ TH1 and TH2 cells during the progression to AIDS may increase the understanding of AIDS pathogenesis. The preferential replication of human immunodeficiency virus (HIV) in either TH1 or TH2 cells could alter the delicate balance of the immune response. TH1 (gamma interferon [IFN-gamma] positive, interleukin-4 [IL-4] and IL-5 negative) and TH2 (IFN-gamma negative, IL-4 and IL-5 positive) clones, developed from several healthy donors, pedigreed by reverse transcriptase PCR (RT-PCR) and enzyme linked immunosorbent assay have similar levels of cell surface expression of CD4 and several chemokine receptor cofactors necessary for viral entry. After activation by specific antigens and infection with T-cell-tropic strains of HIV type 1 (HIV-1), TH1 and TH2 clones showed similar levels of viral entry and reverse transcription. At days 3 through 14 postinfection, HIV replicated to similar levels in several TH1 and TH2 clones as measured by release of HIV p24 and total number of copies of gag RNA/total cell RNA as measured by RT-PCR. When values were normalized for viable cell number in three clones of each type, there was up to twofold more HIV RNA in TH1 than TH2 cells. In addition, several primary monocytotropic HIV-1 strains were able to replicate to similar levels in TH1 and TH2 cells. These studies suggest that the importance of TH1 and TH2 subsets in AIDS pathogenesis transcends clonal differences in their ability to support HIV replication.
对艾滋病进展过程中CD4 + TH1和TH2细胞的发育及功能进行研究,可能会增进对艾滋病发病机制的理解。人类免疫缺陷病毒(HIV)在TH1或TH2细胞中的优先复制,可能会改变免疫反应的微妙平衡。从数名健康供体中分离出的TH1(γ干扰素[IFN-γ]阳性,白细胞介素-4[IL-4]和IL-5阴性)和TH2(IFN-γ阴性,IL-4和IL-5阳性)克隆,通过逆转录酶聚合酶链反应(RT-PCR)和酶联免疫吸附测定进行谱系分析,它们的细胞表面CD4表达水平以及病毒进入所需的几种趋化因子受体辅助因子水平相似。在用特定抗原激活并感染1型嗜T细胞株HIV(HIV-1)后,TH1和TH2克隆显示出相似的病毒进入水平和逆转录水平。在感染后第3至14天,通过HIV p24释放量以及通过RT-PCR测定的gag RNA/总细胞RNA拷贝总数来衡量,HIV在多个TH1和TH2克隆中的复制水平相似。当对每种类型的三个克隆中的活细胞数进行标准化处理后,TH1细胞中的HIV RNA比TH2细胞多两倍。此外,几种原发性嗜单核细胞HIV-1毒株能够在TH1和TH2细胞中以相似的水平进行复制。这些研究表明,TH1和TH2亚群在艾滋病发病机制中的重要性超越了它们支持HIV复制能力的克隆差异。