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

ABSTRACT: Aging profoundly reshapes the immune cell landscape, with particularly strong effects on CD8+ T cells, including a marked decline in naïve cells and the emergence of age-associated GZMK+ CD8+ T cells (TAA cells). Although TAA cells make up a significant fraction of the aged CD8+ T cell compartment, the pathway underlying their differentiation remains unknown. In this study, we demonstrate that TAA cell development is cell-extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a novel TNFΔ69AU/+ mouse model, we show that systemic low-grade inflammation, characteristic of inflammaging, accelerates CD8+ T cell aging and promotes early accumulation of TAA cells. Through detailed analysis of TAA cell heterogeneity, we identified a progenitor subpopulation enriched in the aged adipose tissue. Using heterochronic transplantation, we show that adipose tissue acts as a functional niche, supporting progenitor maintenance and driving the conversion of young CD8+ T cells into the aged phenotype. Taken together, our findings reveal how aging of non-lymphoid tissues orchestrates the reorganization of the CD8+ T cell compartment and highlight adipose tissue as a promising target for therapeutic strategies aimed at modulating immune aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE304476 | GEO | 2026/03/23

REPOSITORIES: GEO

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