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.
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DOI：
10.1126/scitranslmed.abo0686
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发表时间：
2022-06-15
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
--
作者：
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 strikingly abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Further, 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+ GzmB+ CD8 T cells are major cytokine producers with low cytotoxic potential. Using T cell receptor repertoire data, we found that CD8 GzmK+ GzmB+ T cells are clonally expanded in synovial tissues and maintain their granzyme expression and overall cell state in blood, suggesting they are enriched in tissue, but also circulate. Using GzmK and GzmB signatures, we found that GzmK-expressing CD8 T cells were also the major CD8 T cell population in the gut, kidney, and coronavirus disease 2019 (COVID-19) bronchioalveolar lavage fluid, suggesting that they form a core population of tissue-associated T cells across diseases and human tissues. We term this population tissue-enriched expressing GzmK or TteK CD8 cells. Armed to produce cytokines in response to both antigen-dependent and -independent stimuli, CD8 TteK cells have the potential to drive inflammation.
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影响因子：
2.2
作者：
Bengsch B;Ohtani T;Herati RS;Bovenschen N;Chang KM;Wherry EJ
通讯作者：
Wherry EJ
影响因子：
4.4
作者：
Finnegan, A;Grusby, MJ;Zhang, J
通讯作者：
Zhang, J
影响因子：
3.7
作者：
Cooper DM;Pechkovsky DV;Hackett TL;Knight DA;Granville DJ
通讯作者：
Granville DJ
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
9.1
作者：
Cho, Bon-A;Sim, Ji Hyun;Kim, Hang-Rae
通讯作者：
Kim, Hang-Rae