IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells. A role for IL-1 beta in the T cell-independent mechanism of resistance against intracellular pathogens.
IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells. A role for IL-1 beta in the T cell-independent mechanism of resistance against intracellular pathogens.
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DOI：
10.4049/jimmunol.155.9.4347
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发表时间：
1995-11
影响因子：
4.4
通讯作者：
C. Hunter;R. Chizzonite;Jack S. Remington
中科院分区：
文献类型：
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作者：
C. Hunter;R. Chizzonite;Jack S. Remington
患有严重联合免疫缺陷（SCID）的小鼠具有IFN-γ依赖性机制，该机制依赖于IL-12诱导的NK细胞产生IFN-γ，从而抵抗细胞内病原体弓形虫和单核细胞增生李斯特菌。在这份报告中，我们证明了IL-1 β是IL-12刺激NK细胞产生IFN-γ所必需的，并且IL-1在IL-12介导的对T细胞的抗性中是重要的。体内弓形虫用T.弓形虫导致IFN-γ的产生。向这些培养物中加入对IL-1 β特异的中和Ab可完全抑制IFN-γ的产生。LPS或L.使用单核细胞增多症刺激SCID小鼠脾细胞产生IFN-γ。向IL-1 α中加入中和抗体并不影响T刺激的SCID小鼠脾细胞产生IFN-γ。gondii，L.单核细胞增多症或LPS。用IL-1 β或IL-1 α刺激SCID小鼠脾细胞，不产生IFN-γ，但显著增强T.弓形虫或IL-12刺激IFN-γ的产生。此外，用IL-12加TNF-α刺激的SCID小鼠脾细胞产生的IFN-γ被抗IL-1 β完全消除，但不被抗IL-1 α消除。用T.弓形虫或IL-12加TNF-α检测到低水平的IL-1 β;向IFN-γ添加中和Ab导致IL-1 β水平增加5- 10倍。此外，在存在抗IFN-γ的情况下，用IL-12刺激SCID小鼠脾细胞导致IL-1 β的可检测水平增加。为了确定我们的体外数据在体内的相关性，用T.弓形虫感染，并用单独的IL-12或IL-12与对I型IL-1受体特异性的Ab组合治疗。该Ab减少了用T.弓形虫、LPS、L.单核细胞增多症或IL-12加IL-1 β。体内给药该抗体可显著拮抗外源性IL-12延迟T.刚地。（400字处截断摘要）
Mice with the severe combined immunodeficiency (SCID) possess an IFN-gamma-dependent mechanism of resistance to the intracellular pathogens Toxoplasma gondii and Listeria monocytogenes that is dependent on IL-12-induced production of IFN-gamma by NK cells. In this report we demonstrate that IL-1 beta is required for IL-12 to stimulate production of IFN-gamma by NK cells, and that IL-1 is important in IL-12-mediated resistance to T. gondii in vivo. Stimulation of SCID mouse splenocytes with tachyzoites of T. gondii resulted in production of IFN-gamma. Addition of neutralizing Ab specific for IL-1 beta to these cultures inhibited completely the production of IFN-gamma. Similar results were obtained when LPS or L. monocytogenes were used to stimulate production of IFN-gamma by SCID mouse splenocytes. Addition of a neutralizing Ab to IL-1 alpha did not affect production of IFN-gamma by SCID mouse splenocytes stimulated with T. gondii, L. monocytogenes, or LPS. Stimulation of SCID mouse splenocytes with IL-1 beta or IL-1 alpha did not result in production of IFN-gamma but enhanced remarkably the ability of T. gondii or IL-12 to stimulate production of IFN-gamma. Furthermore, production of IFN-gamma by SCID mouse splenocytes stimulated with IL-12 plus TNF-alpha was completely ablated by anti-IL-1 beta, but not by anti-IL-1 alpha. Analysis of the culture supernatants of spleen cells from SCID mice stimulated with T. gondii or IL-12 plus TNF-alpha detected low levels of IL-1 beta; addition of a neutralizing Ab to IFN-gamma resulted in a 5- to 10-fold increase in levels of IL-1 beta. Furthermore, stimulation of SCID mouse splenocytes with IL-12, in the presence of anti-IFN-gamma, resulted in an increase in detectable levels of IL-1 beta. To determine the in vivo relevance of our in vitro data, SCID mice were infected with T. gondii and treated with IL-12 alone or IL-12 in combination with an Ab specific for the type I IL-1 receptor. This Ab reduced production of IFN-gamma by SCID mouse splenocytes stimulated with either T. gondii, LPS, L. monocytogenes, or IL-12 plus IL-1 beta. In vivo administration of this Ab antagonized significantly the ability of exogenous IL-12 to delay the time to death of SCID mice infected with T. gondii.(ABSTRACT TRUNCATED AT 400 WORDS)