Inflammaging in aged tissues drives remodeling of the CD8+ T cell compartment

Aging strongly impacts CD8 + T cells, including the loss of naive cells and the emergence of age-associated GZMK + CD8 + T cells (T AA cells). Although T AA cells constitute a major population in aged mice, the pathway underlying their differentiation remains unknown. Here, we demonstrate that T AA cell development is cell extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a TNF Δ69AU/+ mouse model, we show that low-grade inflammation accelerates CD8 + T cell aging and promotes early accumulation of T AA cells. Analysis of T AA cell heterogeneity further identifies a progenitor subpopulation enriched in the aged adipose tissue. Finally, heterochronic transplantation experiments suggest that the aged adipose tissue can serve as a systemic source of T AA cells and contribute to the conversion of young CD8 + T cells into the aged phenotype. Together, these findings indicate that aged non-lymphoid tissues actively drive CD8 + T cell remodeling and identify adipose tissue as an important niche shaping immune aging.