Chuensirikulchai Kantinan, Pata Supansa, Laopajon Witida, Takheaw Nuchjira, Kotemul Kamonporn, Jindaphun Kanyaruck, Khummuang Saichit, Kasinrerk Watchara
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Immunology. 2024 Oct;173(2):321-338. doi: 10.1111/imm.13826. Epub 2024 Jun 24.
The explicit identification of CD8 T cell subpopulation is important for deciphering the role of CD8 T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE-1H10, recognized two novel subpopulations of peripheral blood CD8 T cells, FE-1H10 and FE-1H10 CD8 T cells. The molecule recognized by mAb FE-1H10 (FE-1H10 molecules) had a higher distribution on effector memory CD8 T cell subsets. The functions of FE-1H10 and FE-1H10 CD8 T cells were investigated. T cell proliferation assays revealed that FE-1H10 CD8 T cells exhibited a higher proliferation rate than FE-1H10 CD8 T cells, whereas FE-1H10 CD8 T cells produced higher levels of IFN-γ and TNF-α than FE-1H10 CD8 T cells. In T cell cytotoxicity assays, FE-1H10 CD8 T cells were able to kill target cells better than FE-1H10 CD8 T cells. RNA-sequencing analysis confirmed that these subpopulations were distinct: FE-1H10 CD8 T cells have higher expression of genes involved in effector functions (IFNG, TNF, GZMB, PRF1, GNLY, FASL, CX3CR1) while FE-1H10 CD8 T cells have greater expression of genes related to memory CD8 T cell populations (CCR7, SELL, TCF7, CD40LG). The results suggested that mAb FE-1H10 identifies two novel distinctive CD8 T cell subpopulations. The FE-1H10 CD8 T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8 T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8 T cells in cancer treatment.
明确鉴定CD8 T细胞亚群对于解读CD8 T细胞在保护机体抵御入侵病原体和癌症方面的作用至关重要。我们制备的单克隆抗体(mAb)名为FE-1H10,可识别外周血CD8 T细胞的两个新亚群,即FE-1H10和FE-1H10 CD8 T细胞。mAb FE-1H10识别的分子(FE-1H10分子)在效应记忆CD8 T细胞亚群上有更高的分布。对FE-1H10和FE-1H10 CD8 T细胞的功能进行了研究。T细胞增殖试验显示,FE-1H10 CD8 T细胞的增殖率高于FE-1H10 CD8 T细胞,而FE-1H10 CD8 T细胞产生的IFN-γ和TNF-α水平高于FE-1H10 CD8 T细胞。在T细胞细胞毒性试验中,FE-1H10 CD8 T细胞比FE-1H10 CD8 T细胞能更好地杀伤靶细胞。RNA测序分析证实这些亚群是不同的:FE-1H10 CD8 T细胞中参与效应功能的基因(IFNG、TNF、GZMB、PRF1、GNLY、FASL、CX3CR1)表达较高,而FE-1H10 CD8 T细胞中与记忆CD8 T细胞群体相关的基因(CCR7、SELL、TCF7、CD40LG)表达较高。结果表明,mAb FE-1H10可识别两个新的独特CD8 T细胞亚群。FE-1H10 CD8 T细胞对肿瘤细胞具有更强的功能。发现这些新的CD8 T细胞亚群可能是癌症治疗中选择潜在CD8 T细胞的最佳免疫疗法的基础知识。