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

Authors
Irina Shchukina, Carlos J. Rodriguez-Hernandez, Heather S. Ruiz, Maksim Kleverov, Rachel L. Mintz, Katsutaka Mineura, Subhadra C. Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A. Mogilenko, Rachael L. Field, Tran H. Nguyen, Quazim A. Alayo, Christopher G. Huckstep, Barbora Vander Wielen, Jonathan R. Brestoff, Sheila A. Stewart, David W. Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J. Randolph, Maxim N. Artyomov


Lab

Journal
Cell Reports

Abstract

Summary

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.

Keywords/Topics
aging; CD8+ T cells; inflammaging; granzyme K; adipose tissue; CP: immunology

BIOSEB Instruments Used:
Bioseb CIS Software (BIO-CIS2),Grip strength test (BIO-GS4),Rotarod for rats and mice (BX-ROD)

Source :

https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00381-5

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