Altered composition of the γδ T cell pool in lymph nodes during ageing enhances tumour growth

Abstract

How age-associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterized the cellular composition of the{gamma}{delta} T cell pool in peripheral lymph nodes (pLNs) upon ageing. We found that ageing has minimal cell-intrinsic effects on function and global gene expression of{gamma}{delta} T cells, and TCR{gamma}{delta} diversity remained stable. However, ageing altered TCR{delta} chain usage and clonal structure of{gamma}{delta} T cell subsets. Importantly, IL-17-producing{gamma}{delta} 17 T cells dominated the{gamma}{delta} T cell pool of aged mice - mainly due to the selective expansion of V{gamma}6+{gamma}{delta} 17 T cells and augmented{gamma}{delta} 17-polarisation of V{gamma}4+ T cells. Expansion of the{gamma}{delta} 17 T cell compartment was supported by increased Interleukin-7 expression in the T cell zone of old mice. In a Lewis lung cancer model, pro-tumourigenic V{gamma}6+{gamma}{delta}17 T cells were exclusively activated in the tumour-draining LN and their infiltration into the tumour correlated with increased tumour size in aged mice. Thus, upon ageing, substantial compositional changes of{gamma}{delta} T cell pool in a dysregulated pLN microenvironment promote tumour growth.