Age-Related Decline in Primary CD8+T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+T Cells

التفاصيل البيبلوغرافية
العنوان: Age-Related Decline in Primary CD8+T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+T Cells
المؤلفون: 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.
المصدر: Cell Reports; June 2018, Vol. 23 Issue: 12 p3512-3524, 13p
مستخلص: 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 TVMcells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TNcells) 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 TVMcells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:22111247
DOI:10.1016/j.celrep.2018.05.057