RNA sequencing of gamma-delta T cell subsets from young and old mice

Organismal ageing is associated with loss of immune function and higher incidence of cancer. Whether the gamma-delta T cell pool changes upon organismal ageing is not known. In this study we have characterized gamma-delta T cells in peripheral lymph nodes from old and young mice. We found that the gamma-delta T cell pool is severely altered in old mice. The IL-17 producing gamma-delta lineage becomes dominating while IFN-gamma producing gamma-delta1 T cells are declining. gamma-deltaTCR sequencing revealed no collapse in diversity but oligoclonal expansions in Vgamma4 gamma-delta17 subsets. Pro-tumourigenic invariant Vgamma6 cells are present only in aged lymph nodes, represent the majority of gamma-delta T cells in the tumour, and are associated with faster tumour progression.机体衰老与免疫功能丧失及癌症发病率升高显著相关。目前尚不明确γδ T细胞（gamma-delta T cell）库是否会随机体衰老发生动态变化。本研究对年轻与老年小鼠外周淋巴结中的γδ T细胞进行了系统表征。结果发现，老年小鼠体内的γδ T细胞库发生了显著重塑：分泌白细胞介素17（IL-17）的γδ T细胞谱系占据主导地位，而分泌干扰素γ（IFN-γ）的γδ1 T细胞数量则显著下降。γδ T细胞受体（TCR）测序结果显示，其细胞多样性并未出现丧失，但Vγ4+ γδ17细胞亚群存在寡克隆扩增现象。促肿瘤发生的恒定型Vγ6细胞仅存在于老年小鼠的淋巴结中，且在肿瘤组织内的γδ T细胞中占比最高，与肿瘤进展加速密切相关。