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 (TAA cells). Although TAA cells constitute a major population in aged mice, the pathway underlying their differentiation remains unknown. Here, we demonstrate that TAA cell development is cell extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a TNFΔ69AU/+ mouse model, we show that low-grade inflammation accelerates CD8+ T cell aging and promotes early accumulation of TAA cells. Analysis of TAA 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 TAA 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.