Diaz-Mitoma F, Kumar A, Karimi S, Kryworuchko M, Daftarian M P, Creery W D, Filion L G, Cameron W
Department of Paediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
Clin Exp Immunol. 1995 Oct;102(1):31-9. doi: 10.1111/j.1365-2249.1995.tb06632.x.
Infection of immune cells with HIV induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. We analysed the expression of T helper type 1 (Th1) (interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) from HIV+ patients. The semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that IFN-gamma mRNA in unstimulated PBL was significantly decreased and IL-10 mRNA was significantly upregulated in patients with < 400 CD4+ T cells/mm3 (n = 30) as compared to patients with > 400 CD4+ T cells/mm3 (n = 6) and normal controls (n = 16). In addition, IL-10 mRNA levels were inversely associated with IFN-gamma expression. Similar results were obtained by measuring IL-10 production in the supernatants of PBL cultured in vitro without stimulation by employing an enzyme immunosorbent assay (ELISA). However, the levels of IL-4 and IFN-gamma produced by unstimulated PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed two groups of HIV+ individuals based on IL-10 production. PBL from one set of individuals produced low levels of IL-10 (low IL-10 producers) whereas the other group produced IL-10 comparable to that of normal controls (IL-10 producers). Production of IL-4 was significantly reduced in HIV+ individuals with < 400 CD4+ T cells/mm3 as compared to the normal controls. However, ability to produce IFN-gamma by mitogen-stimulated total PBL and CD4+ purified cells was not impaired in HIV+ individuals. These results suggest that unstimulated and mitogen-stimulated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis.
HIV感染免疫细胞会导致细胞因子失调，这可能在HIV发病机制中起关键作用。我们分析了HIV阳性患者外周血淋巴细胞（PBL）中1型辅助性T细胞（Th1）（干扰素-γ（IFN-γ））和2型辅助性T细胞（Th2）（IL-4、IL-10）型细胞因子的表达。半定量逆转录聚合酶链反应（RT-PCR）分析显示，与CD4+T细胞>400个/mm3的患者（n = 6）和正常对照（n = 16）相比，CD4+T细胞<400个/mm3的患者（n = 30）未受刺激的PBL中IFN-γ mRNA显著降低，IL-10 mRNA显著上调。此外，IL-10 mRNA水平与IFN-γ表达呈负相关。通过酶联免疫吸附测定（ELISA）检测体外未受刺激培养的PBL上清液中的IL-10产生情况，也得到了类似结果。然而，ELISA检测不到未受刺激的PBL产生的IL-4和IFN-γ水平。丝裂原刺激PBL后，根据IL-10产生情况将HIV阳性个体分为两组。一组个体的PBL产生低水平的IL-10（低IL-10产生者），而另一组产生的IL-10与正常对照相当（IL-10产生者）。与正常对照相比，CD4+T细胞<400个/mm3的HIV阳性个体中IL-4的产生显著减少。然而，HIV阳性个体中丝裂原刺激的总PBL和CD4+纯化细胞产生IFN-γ的能力并未受损。这些结果表明，HIV阳性个体未受刺激和丝裂原刺激的PBL表现出Th2型细胞因子失调，这可能在HIV免疫发病机制中起作用。
