Ravn P, Pedersen B K
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Infect Immun. 1994 Dec;62(12):5305-11. doi: 10.1128/iai.62.12.5305-5311.1994.
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.
多项观察结果表明，非主要组织相容性复合体（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，可能是一种重要的抗微生物防御机制。本研究的目的是调查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成这种细胞毒性发展的方式。用结核菌素纯化蛋白衍生物、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30 - 31 kDa分泌型分枝杆菌蛋白刺激单核细胞后，可诱导非MHC限制的细胞毒性。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 +细胞增殖并表达白细胞介素-2受体。抗原刺激后的去除研究表明，细胞毒性效应细胞为CD16 + CD56 +且CD4 -；单独的CD4 +细胞不介导非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，在抗原刺激前去除血液单核细胞中的CD4 +细胞。当单核细胞在无CD4 +细胞的情况下与纯化蛋白衍生物或短期培养滤液孵育时，细胞毒性活性降低。这种降低可被白细胞介素-2消除，但不能被γ干扰素消除。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。本研究表明，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。
