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Mucosal Immunol. 2015 May;8(3):545-58. doi: 10.1038/mi.2014.87. Epub 2014 Oct 1.

A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.

Author information

1
1] Immunology Section, Lund University, Lund, Sweden [2] Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
2
Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
3
Immunology Section, Lund University, Lund, Sweden.
4
Unit of Airway Inflammation and Immunology, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
5
Department of Urology, Skåne University Hospital, Malmö, Sweden.
6
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
7
Department of Gastroenterology, Skåne University Hospital, Lund, Sweden.
8
1] Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Lund, Sweden [2] LKC Medicine, Nanyang Technological University, Singapore, Singapore.
9
1] Immunology Section, Lund University, Lund, Sweden [2] Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.

Abstract

Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.

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PMID:
25269704
PMCID:
PMC4424383
DOI:
10.1038/mi.2014.87
[Indexed for MEDLINE]
Free PMC Article

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