biostudies-literatureSrinivasan SBLRD VANCATS NIH HHSNIAID NIH HHSNCI NIH HHSNational Institutes of HealthVAU.S. Department of Veterans AffairsNIH HHSe14461https://www.ebi.ac.uk/biostudies/studies/S-EPMC11984669biostudies-literatureUnknown24(4)Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4⁺Foxp3⁺ regulatory T cells (Tregs) have been well documented. However, the nonredundant Foxp3^-CD8⁺ Tregs were never examined in the context of aging. This study first established clear distinctions between phenotypically overlapping CD8⁺ Tregs and virtual memory T cells. Then, we elucidated the dynamics of CD8⁺ Tregs across the lifespan in mice and further extended our investigation to human peripheral blood mononuclear cells (PBMCs). In mice, we discovered a bi-phasic dynamic shift in the frequAging cellAge-Dependent Bi-Phasic Dynamics of Ly49<sup>+</sup>CD8<sup>+</sup> Regulatory T Cell Population.PMC11984669R01 CA288321AI125701R01 AI125701P30 CA054174I01BX005955UL1 TR002645AI177345CA288321I01 BX005955R01 AI177345Fan KKSegura CMa CMukherjee NHuang GMishra SSrinivasan SZhang NIm JRao MWang LfalseAge-Dependent Bi-Phasic Dynamics of Ly49<sup>+</sup>CD8<sup>+</sup> Regulatory T Cell Population.Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4⁺Foxp3⁺ regulatory T cells (Tregs) have been well documented. However, the nonredundant Foxp3^-CD8⁺ Tregs were never examined in the context of aging. This study first established clear distinctions between phenotypically overlapping CD8⁺ Tregs and virtual memory T cells. Then, we elucidated the dynamics of CD8⁺ Tregs across the lifespan in mice and further extended our investigation to human peripheral blood mononuclear cells (PBMCs). In mice, we discovered a bi-phasic dynamic shift in the frequ2025-01-01T00:00:00Z2025 Apr2026-06-01T13:07:21.772Z2026-04-08T12:50:02.655ZS-EPMC119846693969680710.1111/acel.14461