Division of Oral Biology and Oral Medicine, School of Dentistry and Medicine, Los Angeles, CA, USA.
The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry and Medicine, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
Sci Rep. 2020 Nov 23;10(1):20363. doi: 10.1038/s41598-020-76702-1.
Osteoclasts (OCs) and much less dendritic cells (DCs) induce significant expansion and functional activation of NK cells, and furthermore, the OC-expanded NK cells preferentially increase the expansion and activation of CD8+ T cells by targeting CD4+ T cells. When autologous OCs were used to expand patient NK cells much lower percentages of expanded CD8+ T cells, decreased numbers of expanded NK cells and decreased functions of NK cells could be observed, and the addition of allogeneic healthy OCs increased the patients' NK function. Mechanistically, OC-expanded NK cells were found to lyse CD4+ T cells but not CD8+ T cells suggesting potential selection of CD8+ T cells before their expansion by OC activated NK cells. In agreement, Increased IFN-γ secretion, and NK cell-mediated cytotoxicity and higher percentages of CD8+ T cells, in various tissue compartments of oral tumor-bearing hu-BLT mice in response to immunotherapy by OC-expanded NK cells were observed. Thus, our results indicate an important relationship between NK and CD8+ T cells.
破骨细胞（OCs）和较少的树突状细胞（DCs）诱导 NK 细胞的显著扩增和功能激活，此外，OC 扩增的 NK 细胞通过靶向 CD4+T 细胞优先增加 CD8+T 细胞的扩增和激活。当使用自体 OCs 扩增患者的 NK 细胞时，扩增的 CD8+T 细胞的百分比更低，扩增的 NK 细胞数量减少，NK 细胞的功能降低，而添加同种异体健康 OCs 则增加了患者的 NK 功能。从机制上讲，发现 OC 扩增的 NK 细胞裂解 CD4+T 细胞而不是 CD8+T 细胞，这表明 OC 激活的 NK 细胞在其扩增之前可能对 CD8+T 细胞进行了选择。一致地，在口腔肿瘤荷瘤 hu-BLT 小鼠的各种组织隔室中观察到针对 OC 扩增的 NK 细胞的免疫治疗，IFN-γ 分泌增加，NK 细胞介导的细胞毒性增加，CD8+T 细胞的百分比增加。因此，我们的结果表明 NK 和 CD8+T 细胞之间存在重要关系。
