Comparison of key attributes of chronically stimulated CD4+ vs. CD8+ T cells
| Attribute . | Chronically stimulated CD8+ T cells . | Chronically stimulated CD4+ T cells . | References . |
|---|---|---|---|
| IR expression | ↑ PD-1, CTLA4, TIM-3 and LAG-3. ↑2B4, LILRB4 | ↑ PD-1, CTLA4, TIM-3 and LAG-3 | Dow et al. (2013), Goding et al. (2013), Crawford et al. (2014), Pour et al. (2019), Tracy et al. (2022) |
| ↑ CD200 and BTLA4 | |||
| Transcriptional regulation | TOX, NFAT, PRDM1, BACH2, BATF, and EOMES | TOX, NFAT, PRDM1, BACH2, BATF, and EOMES | Crawford et al. (2014), Trefzer et al. (2021), Sumida et al. (2022) |
| Uniquely upregulates IKZF2 (Helios) | |||
| Functional profile | ↓ Self-renew | ↓ Self-renew | Beltra et al. (2020), Fu et al. (2020) |
| ↓ IFNγ, TNFα, and IL2 | ↓ TNFα and IL2 but retains IFNγ, ↑ Tfh attributes (IL21 and IL10) | Crawford et al. (2014), Catakovic et al. (2017), Balança et al. (2021) | |
| Cytotoxicity attributes | ++ to +++ | 0 to ++ | Oh et al. (2020), Liu et al. (2022), Sultan et al. (2024) |
| Epigenetic traits | Characteristic epigenetic remodeling in IR, cytokine, and cytotoxicity genes | ? | Pauken et al. (2016), Schietinger et al. (2016), Stephen et al. (2017), Satpathy et al. (2019) |
| Ontogeny | Terminally exhausted arise from a self-renewing TCF7+ Tpex subset | Arise from a self-renewing TCF7+ progenitor | Beltra et al. (2020), Xia et al. (2022), Zhou et al. (2024) |
| Attribute . | Chronically stimulated CD8+ T cells . | Chronically stimulated CD4+ T cells . | References . |
|---|---|---|---|
| IR expression | ↑ PD-1, CTLA4, TIM-3 and LAG-3. ↑2B4, LILRB4 | ↑ PD-1, CTLA4, TIM-3 and LAG-3 | Dow et al. (2013), Goding et al. (2013), Crawford et al. (2014), Pour et al. (2019), Tracy et al. (2022) |
| ↑ CD200 and BTLA4 | |||
| Transcriptional regulation | TOX, NFAT, PRDM1, BACH2, BATF, and EOMES | TOX, NFAT, PRDM1, BACH2, BATF, and EOMES | Crawford et al. (2014), Trefzer et al. (2021), Sumida et al. (2022) |
| Uniquely upregulates IKZF2 (Helios) | |||
| Functional profile | ↓ Self-renew | ↓ Self-renew | Beltra et al. (2020), Fu et al. (2020) |
| ↓ IFNγ, TNFα, and IL2 | ↓ TNFα and IL2 but retains IFNγ, ↑ Tfh attributes (IL21 and IL10) | Crawford et al. (2014), Catakovic et al. (2017), Balança et al. (2021) | |
| Cytotoxicity attributes | ++ to +++ | 0 to ++ | Oh et al. (2020), Liu et al. (2022), Sultan et al. (2024) |
| Epigenetic traits | Characteristic epigenetic remodeling in IR, cytokine, and cytotoxicity genes | ? | Pauken et al. (2016), Schietinger et al. (2016), Stephen et al. (2017), Satpathy et al. (2019) |
| Ontogeny | Terminally exhausted arise from a self-renewing TCF7+ Tpex subset | Arise from a self-renewing TCF7+ progenitor | Beltra et al. (2020), Xia et al. (2022), Zhou et al. (2024) |
BATF, basic leucine zipper ATF-like transcription factor; EOMES, eomesodermin; BACH2, BTB domain and CNC homolog 2.