Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells
Authors:
- 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.
Details:
Cell Reports, Volume 23, Issue 12, 2018-06-19
Article Link: Click here
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.