Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.
Doctoral School in Systems and Molecular Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Front Immunol. 2022 Jul 14;13:818015. doi: 10.3389/fimmu.2022.818015. eCollection 2022.
Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline (). After stimulation (assessed through plate-bound antibodies against activating receptors or culture in the presence of cytokines such as interleukin (IL)-2 or IL-15) however, they can become cytotoxic and produce cytokines. This is particularly the case in transporter associated with antigen processing (TAP)-deficient mice, which we investigated in the present study. Transporter associated with antigen processing transports endogenous peptides from the cytosol to the endoplasmic reticulum, where they are loaded on nascent MHC class I molecules, which then become stable and expressed at the cell surface. Consequently, TAP-KO mice have very low levels of MHC class I expression. We present a study about phenotypic and functional aspects of NK cells in two mouse strains, C57BL/6 wildtype and TAP1-KO in spleen and lung. We observed that in both types of mice, on the same genetic background, the initial pattern of education, conferred to the cells the inhibitory receptors Ly49C/I and NKG2A, was maintained even after a strong stimulation by the cytokines interleukin-2, interleukin-12, interleukin-15 and interleukin-18. Furthermore, the percentages of activated NK cells expressing Ly49C/I and Ly49I were strongly down-modulated under these conditions. We completed our investigations with phenotypic studies of NK cells from these mice.
自然杀伤 (NK) 细胞是先天免疫系统的重要效应器，参与了对感染和肿瘤的第一道防线。在具有功能之前，这些淋巴细胞必须通过其主要组织相容性复合体 I 类分子与识别它们的自身特异性抑制性受体的相互作用来接受教育或许可。在缺乏这种接触的情况下，要么是由于抑制性受体的表达缺失，要么是由于主要组织相容性复合体 I 类 (MHC I 类) 蛋白的水平非常低，NK 细胞在基线时反应迟钝（）。然而，在受到刺激后（通过针对激活受体的平板结合抗体或在细胞因子如白细胞介素 (IL)-2 或 IL-15 的存在下培养来评估），它们可以变得具有细胞毒性并产生细胞因子。在抗原加工相关转运体 (TAP) 缺陷型小鼠中尤其如此，我们在本研究中对此进行了研究。抗原加工相关转运体将内源性肽从细胞质转运到内质网，在那里它们被加载到新生的 MHC I 类分子上，然后这些分子变得稳定并在细胞表面表达。因此，TAP-KO 小鼠的 MHC I 类表达水平非常低。我们介绍了关于两种小鼠品系（C57BL/6 野生型和 TAP1-KO）脾和肺中 NK 细胞表型和功能方面的研究。我们观察到，在这两种类型的小鼠中，在相同的遗传背景下，赋予细胞抑制性受体 Ly49C/I 和 NKG2A 的初始教育模式，即使在细胞因子白细胞介素-2、白细胞介素-12、白细胞介素-15 和白细胞介素-18 的强烈刺激下也得以维持。此外，在这些条件下，表达 Ly49C/I 和 Ly49I 的激活 NK 细胞的百分比被强烈下调。我们通过对这些小鼠 NK 细胞的表型研究完成了我们的研究。
