Muto Masato, Baghdadi Muhammad, Maekawa Ryuji, Wada Haruka, Seino Ken-Ichiro
Institute for Genetic Medicine, Hokkaido University, Kita15 Nishi7, Sapporo, Hokkaido, 060-0815, Japan.
Cancer Immunol Immunother. 2015 Aug;64(8):941-9. doi: 10.1007/s00262-015-1700-x. Epub 2015 Apr 24.
Human T cells expressing γδ T cell receptor have a potential to show antigen-presenting cell-like phenotype and function upon their activation. However, the mechanisms that underlie the alterations in human γδ T cells remain largely unclear. In this study, we have investigated the molecular characteristics of human γδ T cells related to their acquisition of antigen-presenting capacity in comparison with activated αβ T cells. We found that activated γδ but not αβ T cells upregulated cell surface expression of a scavenger receptor, CD36, which seemed to be mediated by signaling through mitogen-activated protein kinase and/or NF-κB pathways. Confocal microscopical analysis revealed that activated γδ T cells can phagocytose protein antigens. Activated γδ T cells could induce tumor antigen-specific CD8(+) T cells using both apoptotic and live tumor cells as antigen resources. Furthermore, we detected that C/EBPα, a critical transcription factor for the development of myeloid-lineage cells, is expressed much higher in γδ T cells than in αβ T cells. These results unveiled the molecular mechanisms for the elicitation of antigen-presenting functions in γδ T cells and would also help designing new approaches for γδ T cell-mediated human cancer immunotherapy.
表达γδ T细胞受体的人T细胞在激活后有显示出抗原呈递细胞样表型和功能的潜力。然而，人类γδ T细胞变化背后的机制在很大程度上仍不清楚。在本研究中，我们研究了与活化的αβ T细胞相比，人类γδ T细胞获得抗原呈递能力相关的分子特征。我们发现，活化的γδ T细胞而非αβ T细胞上调了清道夫受体CD36的细胞表面表达，这似乎是由丝裂原活化蛋白激酶和/或NF-κB信号通路介导的。共聚焦显微镜分析显示，活化的γδ T细胞能够吞噬蛋白质抗原。活化的γδ T细胞可以使用凋亡和活的肿瘤细胞作为抗原来源诱导肿瘤抗原特异性CD8(+) T细胞。此外，我们检测到C/EBPα，一种髓系细胞发育的关键转录因子，在γδ T细胞中的表达比在αβ T细胞中高得多。这些结果揭示了γδ T细胞中抗原呈递功能引发的分子机制，也将有助于设计γδ T细胞介导的人类癌症免疫治疗的新方法。
