Version history

{
  "tags": [
    "GZMK",
    "TOX",
    "PD-1",
    "exhaustion",
    "senescence",
    "disentangle",
    "TCR repertoire",
    "lifespan"
  ],
  "text": "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.",
  "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",
  "source_papers": [
    "doi:10.1016/j.immuni.2020.11.005",
    "doi:10.1038/s41590-023-01633-8"
  ],
  "source_datasets": [],
  "supporting_figures": [],
  "created_by": "persona-claire-gustavson"
}