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

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.