TABLE 1.
Characteristics of senescent T cells.
| Phenotype | Description | Evidence for phenotype in senescent T cells during human ageing | |
|---|---|---|---|
| CD4+ T cells | CD8+ T cells | ||
| CD27−CD28− | Stimulatory co-receptors CD27 and CD28 are progressively lost during differentiation from naïve to memory T cell subsets | ↑ %CD27−CD28 Moro-García et al. (2013) | ↑ %CD27−CD28− Plunkett et al. (2007) |
| ↑ %CD27−CD28 Henson et al. (2009) | |||
| CD27−CD45RA+ (TEMRA) | CD27 and CD45RA define naïve, TN (27+RA+), central memory, TCM (27+RA−), effector memory, TEM (27−RA-), and senescent, TEMRA (27−RA+) | ↑ %TEMRA Libri et al. (2011) | ↑ %TEMRA Callender et al. (2020) |
| ↑ %TEMRA Callender et al. (2020) | ↑ %TEMRA Riddell et al. (2015) | ||
| SAβGhigh | Senescence-associated β-galactosidase | ↑ % SAβGhigh Martinez-Zamudio et al. (2021) | ↑ %SAβGhigh Martinez-Zamudio et al. (2021) |
| KLRG1+ | Killer Cell Lectin-like Receptor G1, co-inhibitory receptor | TEMRA Di Mitri et al. (2011) | TEMRA Henson et al. (2014) |
| TEMRA Henson et al. (2015) | |||
| TEMRA Pereira et al. (2020) | |||
| CD27−CD28 Henson et al. (2009) | |||
| CD57+ | Terminal differentiation marker | TEMRA Libri et al. (2011) | TEMRA Henson et al. (2014) |
| TEMRA Henson et al. (2015) | |||
| TEMRA Pereira et al. (2020) | |||
| Old donor pan-CD8+ Phadwal et al. (2012) | |||
| NKR+ | Natural Killer Receptors | Old donor pan-CD4+ Alonso-Arias et al. (2011) | TEMRA Pereira et al. (2020) |
| ↑ Cytokine and cytotoxic granule production | Contributor to cytotoxic and inflammatory nature of senescent T cells, e.g., IFNγ, TNFα, perforin, granzyme B | TEMRA Libri et al. (2011) | TEMRA Henson et al. (2014) |
| TEMRA Henson et al. (2015) | |||
| TEMRA Callender et al. (2018) | |||
| ↑ Sestrins | Sestrin-MAPK activation complex (sMAC) drives maladaptive T cell functions and NKR-mediated cytotoxicity | CD27−CD28− Lanna et al. (2017) | CD27−CD28− Pereira et al. (2020) |
| ↓ autophagy | Decreased autophagic flux | Old donor pan-CD4+ Bharath et al. (2020) | CD57+ Phadwal et al. (2012) |
| TEMRA Henson et al. (2014) | |||
| Old donor vaccine-specific cells Alsaleh et al. (2020) | |||
| ↓ proliferative ability | TEMRA Libri et al. (2011) | TEMRA Henson et al. (2014) | |
| TEMRA Henson et al. (2015) | |||
| CD27−CD28− Plunkett et al. (2007) | |||
| ↓ telomerase activity | TEMRA Di Mitri et al. (2011) | TEMRA Henson et al. (2014) | |
| TEMRA Henson et al. (2015) | |||
| CD27−CD28− Plunkett et al. (2007) | |||
| ↓ telomere length | TEMRA Di Mitri et al. (2011) (TEMRA have shorter telomeres than TN) | CD27−CD28− Plunkett et al. (2007) | |
| Old donor pan-CD8+ and TEMRA Sanderson and Simon (2017) | |||
| TEMRA shorter than TN Riddell et al. (2015) | |||
| ↑ γH2AX | TEMRA Di Mitri et al. (2011) | TEMRA Henson et al. (2014) | |
| CD27−CD28− Lanna et al. (2014) | TEMRA Henson et al. (2015) | ||
| TEMRA Callender et al. (2020) | TEMRA Callender et al. (2020) | ||
| ↑ p-ATM (Ser1981) | Phosphorylation/activation of DDR | CD27−CD28− Lanna et al. (2014) | |
| ↑ 53BP1+ | p53-binding protein 1, DNA damage sensor | SAβGhigh Martinez-Zamudio et al. (2021) | |
| ↑ p-p53 (Ser15) | Phosphorylation/activation during DDR | TEMRA Callender et al. (2020) | |
| ↑ ROS | Reactive Oxygen Species | CD27−CD28− Lanna et al. (2014) | TEMRA Henson et al. (2014) |
| Old donor pan-CD8+ Sanderson and Simon (2017) | |||
| ↑ Dysfunctional mitochondria | Old donor pan-CD4+ Bharath et al. (2020) | TEMRA Henson et al. (2014) | |
| TEMRA Callender et al. (2020) | |||