Barcellini W, Rizzardi G P, Borghi M O, Fain C, Lazzarin A, Meroni P L
Institute of Internal Medicine, IRCCS San Raffaele H, University of Milan, Italy.
AIDS. 1994 Jun;8(6):757-62. doi: 10.1097/00002030-199406000-00006.
To study the TH1-->TH2 cytokine switch, thought to occur during the progression of HIV infection.
We investigated interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-negative controls and HIV-positive subjects, stratified according to the Centers for Disease Control and Prevention (CDC) criteria. We correlated the above parameters with markers of disease progression.
Cytokine production was measured in supernatants using enzyme-linked immunosorbent assay (ELISA) in 40 patients and 17 controls. To evaluate disease progression, we also determined CD4+ cell counts, PHA-induced proliferative response, p24 release and spontaneous immunoglobulin (Ig) G and IgM production.
In agreement with the TH1-->TH2 switch hypothesis, we found that in the course of HIV disease mitogen-stimulated IL-2 production decreased, spontaneous and stimulated IL-6 production and spontaneous IL-10 secretion increased; IL-4 showed an increasing trend, although it was reduced in HIV-positive subjects. Finally, immunoglobulin production increased over time. In contrast, mitogen-stimulated IFN-gamma and IL-10 production did not change among the CDC categories, although the former decreased and the latter increased in comparison with HIV-negative controls.
Our data partially agree with the TH1-->TH2 switch hypothesis. Since IL-6 and IL-10 are produced by different cell types, whose proportions and functional features vary in the course of the disease, further experiments with purified lymphocyte subsets and monocytes are required. Nevertheless, as already suggested, we believe that a switch from a type 1 to a type 2 response occurs in HIV infection.
研究被认为发生在HIV感染进程中的TH1向TH2细胞因子转换。
我们调查了来自HIV阴性对照和HIV阳性受试者的经植物血凝素（PHA）刺激和未刺激的外周血单个核细胞（PBMC）培养物中白细胞介素（IL）-2、干扰素（IFN）-γ、IL-4、IL-6和IL-10的产生情况，这些受试者根据疾病控制和预防中心（CDC）的标准进行了分层。我们将上述参数与疾病进展的标志物进行了关联。
使用酶联免疫吸附测定（ELISA）法在40例患者和17例对照的上清液中测量细胞因子的产生。为了评估疾病进展，我们还测定了CD4 +细胞计数、PHA诱导的增殖反应、p24释放以及自发免疫球蛋白（Ig）G和IgM的产生。
与TH1向TH2转换假说一致，我们发现，在HIV疾病进程中，有丝分裂原刺激的IL-2产生减少，自发和刺激的IL-6产生以及自发IL-10分泌增加；IL-4呈上升趋势，尽管在HIV阳性受试者中有所降低。最后，免疫球蛋白的产生随时间增加。相比之下，有丝分裂原刺激的IFN-γ和IL-10产生在CDC分类中没有变化，尽管与HIV阴性对照相比，前者减少而后者增加。
我们的数据部分支持TH1向TH2转换假说。由于IL-6和IL-10由不同细胞类型产生，其比例和功能特征在疾病进程中会发生变化，因此需要对纯化的淋巴细胞亚群和单核细胞进行进一步实验。然而，正如已经指出的，我们认为HIV感染中会发生从1型反应向2型反应的转换。
