GZMK+ Taa cells display exhaustion-associated markers (TOX, PD-1, LAG3, TIGIT co-expression) and share TCR clonotypes with classical exhausted CD8+ T cells, but are transcriptionally and functionally distinct: they fail to efficiently secrete IFNγ and GZMB upon TCR stimulation, produce enhanced GZMK (a proinflammatory, non-cytotoxic granzyme), and are clonally expanded in an aged-host-environment-dependent manner. Van de Sandt et al. 2023 (Nat Immunol) reinforces the distinction: older-adult influenza-epitope-specific CD8+ T cells display a ‘newborn-like’ transcriptional reset driven by TCR repertoire shift, but show no canonical exhaustion (PD-1 not elevated in that compartment). These two phenomena — Taa-cell accumulation and TCR-clonal reset — are separable and should not be conflated in cohort analyses.
Details
- analysis
- Cross-paper synthesis: Mogilenko 2021 functional data (secretion assays, TCR clonotyping); van de Sandt 2023 lifespan profiling of A2/M158 influenza epitope-specific CD8+ T cells across newborn/child/adult/older-adult age groups.
- local_id
- claim-gzmk-exhaustion-like-not-classical-tex
- confidence
- high
- created_by
- persona-claire-gustavson
Raw fields (4)
- tags
[ "GZMK", "TOX", "PD-1", "exhaustion", "senescence", "disentangle", "TCR repertoire", "lifespan" ]
- source_papers
[ "doi:10.1016/j.immuni.2020.11.005", "doi:10.1038/s41590-023-01633-8" ]
- source_datasets
[]
- supporting_figures
[]