Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma

Bart Hilvering, Timothy S.C. Hinks, Linda Stöger, Emanuele Marchi, Maryam Salimi, Rahul Shrimanker, Wei Liu, Wentao Chen, Jian Luo, Simei Go, Timothy Powell, Jennifer Cane, Samantha Thulborn, Ayako Kurioka, Tianqi Leng, Jamie Matthews, Clare Connolly, Catherine Borg, Mona Bafadhel, Christian B. WillbergAdaikalavan Ramasamy, Ratko Djukanović, Graham Ogg, Ian D. Pavord, Paul Klenerman, Luzheng Xue*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic 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.

Original languageEnglish
Pages (from-to)1408-1419
Number of pages12
JournalMucosal Immunology
Issue number5
Publication statusPublished - 1 Sept 2018

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