IL-7-dependent compositional changes within the ?? T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response.

ABSTRACT: How the age-associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterised the cellular composition of the ?? T-cell pool in peripheral lymph nodes (pLNs) upon ageing. We find that ageing has minimal cell-intrinsic effects on function and global gene expression of ?? T cells, and ??TCR diversity remains stable. However, ageing alters TCR? chain usage and clonal structure of ?? T-cell subsets. Importantly, IL-17-producing ??17 T cells dominate the ?? T-cell pool of aged mice-mainly due to the selective expansion of V?6+ ??17 T cells and augmented ??17 polarisation of V?4+ T cells. Expansion of the ??17 T-cell compartment is mediated by increased IL-7 expression in the T-cell zone of old mice. In a Lewis lung cancer model, pro-tumourigenic V?6+ ??17 T cells are exclusively activated in the tumour-draining LN and their infiltration into the tumour correlates with increased tumour size in aged mice. Thus, upon ageing, substantial compositional changes in ?? T-cell pool in the pLN lead to an unbalanced ?? T-cell response in the tumour that is associated with accelerated tumour growth.

SUBMITTER: Chen HC 

PROVIDER: S-EPMC6680116 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature