Abstract
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. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3512-3524 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 23 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 19 Jun 2018 |
Keywords
- aging
- CD8 T cells
- cellular senescence
- exhaustion
- naive CD8 T cells
- T cell dysfunction
- virtual memory T cells
Cite this
}
Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells. / 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.
In: Cell Reports, Vol. 23, No. 12, 19.06.2018, p. 3512-3524.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells
AU - Quinn, Kylie M.
AU - Fox, Annette
AU - Harland, Kim L.
AU - Russ, Brendan E.
AU - Li, Jasmine
AU - Nguyen, Thi H.O.
AU - Loh, Liyen
AU - Olshanksy, Moshe
AU - Naeem, Haroon
AU - Tsyganov, Kirill
AU - Wiede, Florian
AU - Webster, Rosela
AU - Blyth, Chantelle
AU - Sng, Xavier Y.X.
AU - Tiganis, Tony
AU - Powell, David
AU - Doherty, Peter C.
AU - Turner, Stephen J.
AU - Kedzierska, Katherine
AU - La Gruta, Nicole L.
PY - 2018/6/19
Y1 - 2018/6/19
N2 - 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. 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.
AB - 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. 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.
KW - aging
KW - CD8 T cells
KW - cellular senescence
KW - exhaustion
KW - naive CD8 T cells
KW - T cell dysfunction
KW - virtual memory T cells
UR - http://www.scopus.com/inward/record.url?scp=85048256953&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.05.057
DO - 10.1016/j.celrep.2018.05.057
M3 - Article
VL - 23
SP - 3512
EP - 3524
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 12
ER -