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Quinn, Kylie M.; Fox, Annette; Harland, Kim L.; Russ, Brendan E.; Li, Jasmine; Nguyen, Thi H.O.; Loh, Liyen; Olshanksy, Moshe; Naeem, Haroon; Tsyganov, Kirill; Wiede, Florian; Webster, Rosela; Blyth, Chantelle; Sng, Xavier Y.X.; Tiganis, Tony; Powell, David; Doherty, Peter C.; Turner, Stephen J.; Kedzierska, Katherine; La Gruta, Nicole L.
Cell reports, 06/2018, Letnik: 23, Številka: 12Journal Article
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. Display omitted •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 CD8 T cell responses decline with age, but virtual memory T (TVM) cells accumulate. Quinn et al. demonstrate that TVM cells lose the ability to proliferate in response to TCR signals, but not IL-15, with increasing age. Aged TVM cells express transcriptional and phenotypic markers of senescence, rather than exhaustion.
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