IL-12 inhibits the production of IL-4 and IL-10 in allergen-specific human CD4+ T lymphocytes.
IL-12 inhibits the production of IL-4 and IL-10 in allergen-specific human CD4+ T lymphocytes.
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DOI：
10.4049/jimmunol.155.1.111
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发表时间：
1995-07
影响因子：
4.4
通讯作者：
J. Marshall;H. Secrist;R. DeKruyff;S. Wolf;D. Umetsu
中科院分区：
文献类型：
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作者：
J. Marshall;H. Secrist;R. DeKruyff;S. Wolf;D. Umetsu
IL-12 通过增强 IFN-γ 合成和增强 Th1 细胞的发育来影响未引发的 CD4+ T 细胞中的细胞因子合成，但其对 Ag 引发的 T 细胞（被认为具有相对固定的细胞因子谱）的影响尚不清楚。我们研究了体外刺激后，IL-12 改变来自过敏供体的过敏原特异性人 CD4+ T 淋巴细胞细胞因子合成的能力。 CD4+ T 细胞从过敏性鼻炎受试者的外周血中获取，去除活化的 T 细胞，并与 APC 和过敏原一起培养。 IL-12显着抑制IL-4和IL-10合成的发展，同时增强T细胞分泌IFN-γ和IL-2，并增强Ag特异性T细胞增殖。 IL-12对IL-4合成的抑制作用不依赖于IFN-γ的存在，在培养开始时添加IL-12时抑制作用最大，而在培养后期添加时抑制作用最小，表明静息记忆CD4+T细胞比活化的CD4+T细胞对IL-12的作用更敏感。 IL-12 对 IL-4 和 IL-10 合成的影响不依赖于 APC 类型，因为当 B 细胞或单核细胞充当 APC 时，IL-12 会减少 IL-4 合成。这些结果表明，IL-12可能对治疗过敏性疾病有治疗作用，其中过敏原特异性T细胞特征性地产生增加量的IL-4和IL-10。
IL-12 influences cytokine synthesis in unprimed CD4+ T cells by enhancing IFN-gamma synthesis and enhancing the development of Th1 cells, but its effects upon Ag-primed T cells, which are thought to have relatively fixed cytokine profiles, is less clear. We investigated the capacity of IL-12 to modify cytokine synthesis in allergen-specific human CD4+ T lymphocytes from allergic donors after in vitro stimulation. CD4+ T cells were obtained from the peripheral blood of subjects with allergic rhinitis, depleted of activated T cells, and cultured with APCs and allergen. IL-12 dramatically inhibited the development of IL-4 and IL-10 synthesis, while it enhanced T cell secretion of IFN-gamma and IL-2, and enhanced Ag-specific T cell proliferation. The inhibitory effect of IL-12 on IL-4 synthesis was not dependent on the presence of IFN-gamma, was greatest when IL-12 was added at the initiation of culture, and was minimal when added late, indicating that resting memory CD4+ T cells were more sensitive than activated CD4+ T cells to the effects of IL-12. The effect of IL-12 on IL-4 and IL-10 synthesis was not dependent on the APC type, because IL-12 decreased IL-4 synthesis when either B cells or monocytes served as APCs. These results indicate that IL-12 may be therapeutically beneficial in the treatment of allergic diseases in which allergen-specific T cells characteristically produce enhanced quantities of IL-4 and IL-10.