鉴定人源细胞为 CD16CD56 细胞毒性 CD4 T 细胞。
Identification of human exT cells as CD16CD56 cytotoxic CD4 T cells.
机构信息
La Jolla Institute for Immunology, La Jolla, CA, USA.
Immunology Center of Georgia, Augusta University, Augusta, GA, USA.
出版信息
Nat Immunol. 2023 Oct;24(10):1748-1761. doi: 10.1038/s41590-023-01589-9. Epub 2023 Aug 10.
In atherosclerosis, some regulatory T (T) cells become exT cells. We crossed inducible T and exT cell lineage-tracker mice (FoxP3ROSA26) to atherosclerosis-prone Apoe mice, sorted T cells and exT cells and determined their transcriptomes by bulk RNA sequencing (RNA-seq). Genes that were differentially expressed between mouse T cells and exT cells and filtered for their presence in a human single-cell RNA-sequencing (scRNA-seq) panel identified exT cell signature genes as CST7, NKG7, GZMA, PRF1, TBX21 and CCL4. Projecting these genes onto the human scRNA-seq with CITE-seq data identified human exT cells as CD3CD4CD16CD56, which was validated by flow cytometry. Bulk RNA-seq of sorted human exT cells identified them as inflammatory and cytotoxic CD4T cells that were significantly distinct from both natural killer and T cells. DNA sequencing for T cell receptor-β showed clonal expansion of T cell CDR3 sequences in exT cells. Cytotoxicity was functionally demonstrated in cell killing and CD107a degranulation assays, which identifies human exT cells as cytotoxic CD4T cells.
在动脉粥样硬化中，一些调节性 T（T）细胞变成了效应 T（exT）细胞。我们将诱导型 T 和 exT 细胞谱系示踪小鼠（FoxP3ROSA26）与易患动脉粥样硬化的 Apoe 小鼠杂交，分选 T 细胞和 exT 细胞，并通过批量 RNA 测序（RNA-seq）测定它们的转录组。在人与单细胞 RNA 测序（scRNA-seq）面板之间差异表达的基因被筛选出来，这些基因存在于人类单细胞 RNA 测序（scRNA-seq）面板中，鉴定出 exT 细胞特征基因作为 CST7、NKG7、GZMA、PRF1、TBX21 和 CCL4。将这些基因投射到人类 scRNA-seq 上，并与 CITE-seq 数据一起识别出人类 exT 细胞为 CD3+CD4+CD16+CD56+，这通过流式细胞术得到了验证。分选后的人类 exT 细胞的批量 RNA-seq 鉴定出它们是炎症性和细胞毒性 CD4T 细胞，与自然杀伤细胞和 T 细胞明显不同。T 细胞受体-β 的 DNA 测序显示 exT 细胞中 T 细胞 CDR3 序列的克隆扩增。在细胞杀伤和 CD107a 脱颗粒测定中证明了细胞毒性，这鉴定出人类 exT 细胞为细胞毒性 CD4T 细胞。
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