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Peer-reviewedCC BY 4.0Frontiers in Immunology

Reconciling CD8 T cell subsets: GZMK+, cytotoxic, resident memory, exhausted, and other CD8 T cells in blood and tissue

  1. 1Division of Rheumatology, Department of Medicine, University of Colorado Anschutz

Abstract

CD8 T cells represent a large portion of lymphocytes in blood as well as in inflamed tissues. Recent studies have shed new light on the populations present in tissues during health and disease, prompting a re-evaluation of the roles CD8 T cells can play in human pathophysiology. Inconsistent and overlapping CD8 T cell subset nomenclature and definitions present current challenges in the field and a barrier to interpreting the literature. In this review, we discuss CD8 T cell subsets in blood and tissues, including markers, phenotypes, and migration patterns. We also address intersections among these populations, including areas of ambiguity that warrant further research. To simplify the analysis of human RNA-seq datasets from sites of disease, we propose that stratifying cells by expression of granzyme B (GZMB) versus granzyme K (GZMK) provides a useful framework that emphasizes effector function phenotypes. We lastly summarize disease associations for granzyme B- and granzyme K-expressing CD8 T cell subsets.

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BibTeX
@article{mickens2026reconciling,
  title = {{Reconciling CD8 T cell subsets: GZMK+, cytotoxic, resident memory, exhausted, and other CD8 T cells in blood and tissue}},
  author = {Kaylee L. Mickens and Anna Helena Jonsson},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1905956},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1905956/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Reconciling CD8 T cell subsets: GZMK+, cytotoxic, resident memory, exhausted, and other CD8 T cells in blood and tissue
AU  - Kaylee L. Mickens
AU  - Anna Helena Jonsson
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1905956
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1905956/full
AB  - CD8 T cells represent a large portion of lymphocytes in blood as well as in inflamed tissues. Recent studies have shed new light on the populations present in tissues during health and disease, prompting a re-evaluation of the roles CD8 T cells can play in human pathophysiology. Inconsistent and overlapping CD8 T cell subset nomenclature and definitions present current challenges in the field and a barrier to interpreting the literature. In this review, we discuss CD8 T cell subsets in blood and tissues, including markers, phenotypes, and migration patterns. We also address intersections among these populations, including areas of ambiguity that warrant further research. To simplify the analysis of human RNA-seq datasets from sites of disease, we propose that stratifying cells by expression of granzyme B (GZMB) versus granzyme K (GZMK) provides a useful framework that emphasizes effector function phenotypes. We lastly summarize disease associations for granzyme B- and granzyme K-expressing CD8 T cell subsets.
SN  - 1664-3224
ER  -