RT Journal Article SR Electronic T1 Type-2 CD8+ T lymphocytes responsive to PGD2 and LTE4 in severe eosinophilic asthma JF bioRxiv FD Cold Spring Harbor Laboratory SP 247171 DO 10.1101/247171 A1 Bart Hilvering A1 Timothy SC Hinks A1 Linda Stöger A1 Emanuele Marchi A1 Maryam Salimi A1 Rahul Shrimanker A1 Wei Liu A1 Wentao Chen A1 Jian Luo A1 Simei Go A1 Timothy Powell A1 Jennifer Cane A1 Samantha Thulborn A1 Ayako Kurioka A1 Tianqi Leng A1 Jamie Matthews A1 Clare Connolly A1 Catherine Borg A1 Mona Bafadhel A1 Christian B Willberg A1 Adaikalavan Ramasamy A1 Ratko Djukanović A1 Graham Ogg A1 Ian D Pavord A1 Paul Klenerman A1 Luzheng Xue YR 2018 UL http://biorxiv.org/content/early/2018/01/12/247171.abstract AB The functions and in vivo roles of type-2 CD8+ T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.