PT  - JOURNAL ARTICLE
AU  - Hung-Chang Chen
AU  - Nils Eling
AU  - Celia Pilar Martinez-Jimenez
AU  - Louise McNeill O’Brien
AU  - John C. Marioni
AU  - Duncan T. Odom
AU  - Maike de la Roche
TI  - Altered composition of the <em>γδ</em> T cell pool in lymph nodes during ageing enhances tumour growth
AID  - 10.1101/480327
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 480327
4099  - http://biorxiv.org/content/early/2018/11/27/480327.short
4100  - http://biorxiv.org/content/early/2018/11/27/480327.full
AB  - How age-associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterized the cellular composition of the γδ 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 γδ T cells, and TCRγδ diversity remained stable. However, ageing altered TCRδ chain usage and clonal structure of γδ T cell subsets. Importantly, IL-17-producing γδ17 T cells dominated the γδ T cell pool of aged mice - mainly due to the selective expansion of Vγ6+ γδ17 T cells and augmented γδ17-polarisation of Vγ4+ T cells. Expansion of the γδ17 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 Vγ6+γδ17 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 γδ T cell pool in a dysregulated pLN microenvironment promote tumour growth.