首页> 外文期刊>Infection and immunity >Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens.
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Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens.

机译:非主要组织相容性复合物限制了分泌的分枝杆菌蛋白和其他分枝杆菌抗原刺激的血液单核细胞的细胞毒活性。

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Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate the influences of different mycobacterial antigens on non-MHC-restricted cytotoxicity and further to investigate the ways by which various lymphocyte subpopulations contribute to the development of this cytotoxicity. Non-MHC-restricted cytotoxicity was induced following stimulation of mononuclear cells with tuberculin purified protein derivative, Mycobacterium bovis bacillus Calmette-Guérin (BCG), short- and long-term culture filtrates of virulent Mycobacterium tuberculosis H37Rv, and 30-31-kDa secreted mycobacterial protein. These antigens also induced proliferation and production of gamma interferon. The CD4+ cells proliferated and expressed interleukin-2 receptors following stimulation with mycobacterial antigens. Depletion studies after antigen stimulation showed that the cytotoxic effector cells were CD16+ CD56+ and CD4-; the CD4+ cells alone did not mediate non-MHC-restricted cytotoxicity. To evaluate the influence of CD4+ cells on the development of non-MHC-restricted cytotoxicity, blood mononuclear cells were depleted of CD4+ cells before antigen stimulation. When mononuclear cells were incubated with purified protein derivative or short-term culture filtrate in the absence of CD4+ cells, cytotoxic activity was reduced. This reduction was abolished by interleukin-2 but not by gamma interferon. We conclude that several mycobacterial antigens are able to induce non-MHC-restricted cytotoxicity. This study indicates that non-MHC-restricted cytotoxicity following stimulation with mycobacterial antigens is induced by cytokines released by antigen-specific activated CD4+ cells.
机译:一些观察结果表明,非主要的组织相容性复合物(MHC)限制的细胞毒性(例如由自然杀伤细胞和淋巴因子激活的杀伤细胞介导的)可能是重要的抗菌防御机制。本研究的目的是研究不同分枝杆菌抗原对非MHC限制的细胞毒性的影响,并进一步研究各种淋巴细胞亚群促进这种细胞毒性发展的方式。结核菌素纯化的蛋白衍生物,牛分枝杆菌卡介苗(BCG),强毒结核分枝杆菌H37Rv的短期和长期培养滤液以及分泌的30-31-kDa刺激单核细胞后,诱导非MHC限制的细胞毒性分枝杆菌蛋白。这些抗原还诱导γ干扰素的增殖和产生。用分枝杆菌抗原刺激后,CD4 +细胞增殖并表达白介素2受体。抗原刺激后的耗竭研究表明,细胞毒性效应细胞为CD16 + CD56 +和CD4-。仅CD4 +细胞不会介导非MHC限制的细胞毒性。为了评估CD4 +细胞对非MHC限制的细胞毒性发展的影响,在抗原刺激之前先将血液单核细胞中的CD4 +细胞清除掉。在不存在CD4 +细胞的情况下,将单核细胞与纯化的蛋白衍生物或短期培养滤液一起孵育时,细胞毒性降低。白介素2消除了这种减少,但γ干扰素没有消除。我们得出结论,几种分枝杆菌抗原能够诱导非MHC限制的细胞毒性。这项研究表明,分枝杆菌抗原刺激后非MHC限制的细胞毒性是由抗原特异性活化的CD4 +细胞释放的细胞因子诱导的。

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