BRUCELLA-ABORTUS INDUCES A NOVEL CYTOKINE GENE-EXPRESSION PATTERN CHARACTERIZED BY ELEVATED IL-10 AND IFN-GAMMA IN CD4+ T-CELLS
BRUCELLA-ABORTUS INDUCES A NOVEL CYTOKINE GENE-EXPRESSION PATTERN CHARACTERIZED BY ELEVATED IL-10 AND IFN-GAMMA IN CD4+ T-CELLS
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DOI：
10.1093/intimm/5.8.877
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发表时间：
1993-08-01
影响因子：
4.4
通讯作者：
GAUSE, WC
中科院分区：
文献类型：
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作者：
SVETIC, A;JIAN, YC;GAUSE, WC
先前已证明用灭活的流产布鲁氏菌 (BA) 免疫 BALB/c 小鼠可增加血清 IgG2a 水平，并且这些小鼠的长期 T 细胞克隆会分泌 T(h)1 相关细胞因子：IFN-γ 和 IL-2，但不包括 IL-4 或 IL-5。我们分析了 BA 初次免疫后的细胞因子基因表达，以确定 CD4+ T 细胞何时首次表达细胞因子基因，以及是否可以在 T(h)1 样模式之前识别特定的假设细胞因子模式（例如 T(h) 前体、T(h)0）。我们的结果证明了 T(h)1/T(h)2 细胞因子基因表达的高度一致和新颖的模式，其特征是 CD4+ T 细胞中 IL-10 和 IFN-γ 升高，这种模式迅速表现出来，并在免疫后持续至少 10 天。没有观察到 IL-2 细胞因子基因表达的升高，并且用阻断性抗 IL-2 抗体治疗 BA 免疫小鼠对细胞因子基因表达模式没有影响，尽管用抗 IFN 抗体治疗导致 IL-4、IL-5 和 IL-9 细胞因子基因表达增加，而早在 4 天后 IFN-γ 或 IL-10 没有任何变化 免疫接种。这些结果表明，在没有升高的 IL-2 的情况下，整个病原体可能会触发足够的共刺激信号来快速诱导效应 T 细胞，并且 IL-10 在某些 T(h)1 样反应中会特异性升高。
Immunization of BALB/c mice with killed Brucella abortus (BA) has previously been shown to increase serum IgG2a levels and long-term T cell clones from these mice secrete T(h)1-associated cytokines: IFN-gamma and IL-2 but not IL-4 or IL-5. We analyzed cytokine gene expression following primary immunization with BA to determine when CD4+ T cells first express cytokine genes and whether specific hypothesized cytokine patterns (e.g. T(h) precursor, T(h)0) could be identified prior to a T(h)1-like pattern. Our results demonstrated a highly consistent and novel pattern of T(h)1/T(h)2 cytokine gene expression characterized by elevated IL-10 and IFN-gamma in CD4+ T cells which rapidly manifests itself and is sustained for at least 10 days after immunization. No elevation in IL-2 cytokine gene expression was observed and treatment of BA-immunized mice with blocking anti-IL-2 antibodies had no effect on the cytokine gene expression pattern, although treatment with anti-IFN antibodies resulted in increased IL-4, IL-5, and IL-9 cytokine gene expression, in the absence of any change in IFN-gamma or IL-10 as early as 4 days after immunization. These results suggest that a whole pathogen may trigger sufficient costimulatory signals to rapidly induce effector T cells in the absence of elevated IL-2 and that IL-10 is specifically elevated in certain T(h)1-like responses.