Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells.
Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells.
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干扰素α增加了产生干扰素伽玛的人CD4+ T细胞的频率。
DOI：
10.1084/jem.178.5.1655
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发表时间：
1993-11-01
影响因子：
15.3
通讯作者：
Heusser, C H
中科院分区：
文献类型：
--
作者：
Brinkmann, V;Geiger, T;Alkan, S;Heusser, C H
辅助性T型2 (Th2)-与th1样细胞的比例增加有助于过敏性疾病和许多慢性感染（包括艾滋病）的免疫失调。th2型免疫反应的特征是th2细胞产生白细胞介素-4 （IL-4）水平升高和干扰素- γ (IFN- γ)水平降低。Th1-或th2样表型的诱导可能受到抗原呈递细胞及其细胞因子（如ifn - α）的严格控制。在这项研究中，我们确定了随机选择的健康个体外周血中潜在的IL-4和/或ifn - γ产生T细胞的频率，并分析了ifn - α是否控制IL-4和/或ifn - γ的产生。在存在或不存在ifn - α的情况下，通过T细胞受体/CD3复合物刺激纯化的CD4+或CD8+ T细胞24小时，酶联免疫斑点法检测到单个IL-4和ifn - γ分泌细胞。在缺乏ifn - α的情况下，CD4细胞产生ifn - γ的频率为1:50-300，产生IL-4的频率为1:110-<1:10万。在CD4细胞激活过程中加入ifn - α增加了ifn - γ mRNA的水平。结果，产生ifn - γ的CD4细胞的数量和分泌ifn - γ的数量增加了10倍。相比之下，ifn - α并没有增加分泌il -4的CD4细胞的频率。在缺乏ifn - α的情况下，向CD4细胞中添加外源性IL-4可抑制70%的ifn - γ分泌。然而，当ifn - α存在时，IL-4没有表现出任何抑制作用。与CD4细胞相比，CD8细胞产生ifn - γ的频率更高（1:5-10），而产生IL-4的频率更低（1:5 300至< 1:10万）。ifn - α对CD8细胞产生ifn - γ或IL-4的频率没有任何影响。综上所述，结果表明IFN- α增加了分泌IFN- γ的CD4 Th细胞的频率，并拮抗IL-4对IFN- γ产生的抑制作用。因此，ifn - α可能有利于诱导和维持Th1样细胞，从而抵消th2驱动的过敏性免疫反应。
An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon gamma (IFN- gamma). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-alpha. In this study we have determined the frequencies of potential IL-4- and/or IFN-gamma-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-alpha controls IL-4 and/or IFN-gamma production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-alpha, and single IL-4- and IFN-gamma-secreting cells were detected in enzyme- linked immunospot assays. In the absence of IFN-alpha, CD4 cells produced IFN-gamma at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-alpha during the activation of CD4 cells increased the levels of IFN-gamma mRNA. As a consequence, the numbers of IFN-gamma-producing CD4 cells and the amounts of secreted IFN-gamma increased 10-fold. In contrast, IFN-alpha did not increase the frequency of IL-4-secreting CD4 cells. In the absence of IFN-alpha, addition of exogenous IL-4 to cultures of CD4 cells suppressed IFN-gamma secretion by 70%. However, in the presence of IFN-alpha, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-gamma more frequently (1:5-10) but IL-4 less frequently (1:5,300 to < 1:100,000). IFN-alpha did not display any effect on the frequency of either IFN-gamma or IL-4 production by CD8 cells. Taken together the results indicate that IFN- alpha increases the frequency of IFN-gamma-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-gamma production. As a consequence, IFN-alpha may favor the induction and maintenance of Th1- like cells and thereby counteract Th2-driven allergic immune responses.