Population

Biology

Molecular biology

Cytotoxic T cell

Granzyme

Chemistry

In vitro

Immunology

Perforin

Granzyme B

Cell biology

Biochemistry

Medicine

Immune system

Environmental health

Science Translational Medicine

T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin. Functional experiments demonstrate that these GzmK

Granzyme K <sup>+</sup> CD8 T cells form a core population in inflamed human tissue

Granzyme K + CD8 T cells form a core population in inflamed human tissue

Granzyme K ⁺ CD8 T cells form a core population in inflamed human tissue