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Cord blood CD8+ t cells have a natural propensity to express IL-4 in a fatty acid metabolism and caspase activation-dependent manner

Zhang, Yuxia, Maksimovic, Jovana, Huang, Bing, De Souza, David Peter, Naselli, Gaetano, Chen, Huan, Zhang, Li, Weng, Kai, Liang, Hanquan, Xu, Yanhui, Wentworth, John M., Huntington, Nicholas D., Oshlack, Alicia, Gong, Sitang, Kallies, Axel, Vuillermin, Peter, Yang, Min and Harrison, Leonard C. 2018, Cord blood CD8+ t cells have a natural propensity to express IL-4 in a fatty acid metabolism and caspase activation-dependent manner, Frontiers in immunology, vol. 9, doi: 10.3389/fimmu.2018.00879.

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Title Cord blood CD8+ t cells have a natural propensity to express IL-4 in a fatty acid metabolism and caspase activation-dependent manner
Author(s) Zhang, Yuxia
Maksimovic, Jovana
Huang, Bing
De Souza, David Peter
Naselli, Gaetano
Chen, Huan
Zhang, Li
Weng, Kai
Liang, Hanquan
Xu, Yanhui
Wentworth, John M.
Huntington, Nicholas D.
Oshlack, Alicia
Gong, Sitang
Kallies, Axel
Vuillermin, PeterORCID iD for Vuillermin, Peter orcid.org/0000-0002-6580-0346
Yang, Min
Harrison, Leonard C.
Journal name Frontiers in immunology
Volume number 9
Article ID 879
Total pages 13
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2018-04-25
ISSN 1664-3224
Keyword(s) CD8+ T cell
IL-4
caspases
fatty acid oxidation
glycolysis
Science & Technology
Life Sciences & Biomedicine
Immunology
CD8(+) T cell
RESPONSES
DIFFERENTIATION
INTERLEUKIN-2
APOPTOSIS
POLARIZATION
LYMPHOCYTES
POPULATIONS
GENERATION
INFECTION
NEWBORNS
Summary How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children.
Language eng
DOI 10.3389/fimmu.2018.00879
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018 Zhang, Maksimovic, Huang, De Souza, Naselli, Chen, Zhang, Weng, Liang, Xu, Wentworth, Huntington, Oshlack, Gong, Kallies, Vuillermin, Yang and Harrison
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30110516

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.