Cell Reports
Volume 23, Issue 12, 19 June 2018, Pages 3512-3524
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Article
Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells

https://doi.org/10.1016/j.celrep.2018.05.057Get rights and content
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Highlights

  • Aged TVM cells exhibit a defect in proliferation with TCR, but not IL-15, signaling

  • Transfer of aged CD8 T cells to a young environment cannot recover the TVM defect

  • By contrast, TN cells show a marked retention of proliferative capacity with age

  • Aged TVM cells exhibit a profile consistent with senescence, not exhaustion

Summary

Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated “virtual memory” (TVM) cells, but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TN cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged TVM cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population.

Keywords

aging
virtual memory T cells
CD8+ T cells
cellular senescence
T cell dysfunction
naive CD8+ T cells
exhaustion

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