D'Orazio J A, Cole B C, Stein-Streilein J
Department of Microbiology and Immunology, University of Miami School of Medicine 33101, USA.
Infect Immun. 1996 Feb;64(2):441-7. doi: 10.1128/iai.64.2.441-447.1996.
While the effects of superantigens on T lymphocytes are well characterized, how superantigens interact with other immune cells is less clear. This report examines the effects of Mycoplasma arthritidis mitogen (MAM) on human natural killer (NK) cell activity. Incubation of peripheral blood mononuclear cells (PBMC) with MAM for 16 to 20 h augmented NK cytotoxicity (against K562) in a dose-dependent manner (P < or = 0.05). Superantigen-dependent cellular cytotoxicity, an activity of superantigen-activated cytotoxic T cells, was not involved in lysis of K562 cells because the erythroleukemic tumor target cells expressed no class II major histocompatibility complex by fluorescence-activated cell sorter analysis. Kinetic experiments showed that the largest increase in NK activity induced by MAM occurred within 48 h. Incubation with MAM caused a portion of NK cells to become adherent to tissue culture flasks, a quality associated with activation, and augmented NK activity was found in both adherent and nonadherent subpopulations. Experiments using cytokine-specific neutralizing antibodies showed that interleukin-2 contributed to enhancement of the NK activity observed in superantigen-stimulated PBMC. Interestingly, MAM was able to augment NK lysis of highly purified NK (CD56+) cells in the absence of other immune cells in 9 of 12 blood specimens, with the augmented lytic activity ranging from 110 to 170% of unstimulated NK activity. In summary, data presented in this report show for the first time that MAM affects human NK cells directly by increasing their lytic capacity and indirectly in PBMC as a consequence of cytokines produced by T cells. Results of this work suggest that, in vivo, one consequence of interaction with superantigen-secreting microorganisms may be up-regulation of NK lytic activity. These findings may have clinical application as a means of generating augmented NK effector cells useful in the immunotherapy of parasitic infections or neoplasms.
虽然超抗原对T淋巴细胞的作用已得到充分表征，但超抗原与其他免疫细胞如何相互作用尚不清楚。本报告研究了关节炎支原体有丝分裂原（MAM）对人自然杀伤（NK）细胞活性的影响。外周血单个核细胞（PBMC）与MAM孵育16至20小时后，NK细胞毒性（针对K562）呈剂量依赖性增强（P≤0.05）。超抗原依赖性细胞毒性是超抗原激活的细胞毒性T细胞的一种活性，不参与K562细胞的裂解，因为通过荧光激活细胞分选分析，红白血病肿瘤靶细胞不表达II类主要组织相容性复合体。动力学实验表明，MAM诱导的NK活性最大增加发生在48小时内。与MAM孵育导致一部分NK细胞黏附于组织培养瓶，这一特性与激活相关，并且在黏附亚群和非黏附亚群中均发现NK活性增强。使用细胞因子特异性中和抗体的实验表明，白细胞介素-2有助于增强在超抗原刺激的PBMC中观察到的NK活性。有趣的是，在12份血液标本中的9份中，MAM能够在不存在其他免疫细胞的情况下增强高度纯化的NK（CD56 +）细胞的NK裂解作用，增强的裂解活性为未刺激的NK活性的110%至170%。总之，本报告中的数据首次表明，MAM通过增加其裂解能力直接影响人NK细胞，并通过T细胞产生的细胞因子间接影响PBMC中的NK细胞。这项工作的结果表明，在体内，与分泌超抗原的微生物相互作用的一个后果可能是NK裂解活性的上调。这些发现可能具有临床应用价值，可作为一种产生增强的NK效应细胞的方法，用于寄生虫感染或肿瘤的免疫治疗。
