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

Holmkvist, Petra LU ; Roepstorff, K ; Uronen-Hansson, Heli LU ; Sandén, Caroline LU ; Gudjonsson, Sigurdur LU ; Hultman Patschan, Oliver LU ; Grip, Olof LU ; Marsal, Jan LU ; Schmidtchen, Artur LU and Hornum, L , et al. (2015) In Mucosal Immunology 8(3). p.545-558
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... (More)
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.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
8
issue
3
pages
545 - 558
publisher
Elsevier
external identifiers
  • pmid:25269704
  • wos:000354085700010
  • scopus:84928910445
  • pmid:25269704
ISSN
1933-0219
DOI
10.1038/mi.2014.87
language
English
LU publication?
yes
id
9d152b41-fd9a-4052-b80a-07e23700c3d3 (old id 4738687)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25269704?dopt=Abstract
date added to LUP
2016-04-01 10:40:08
date last changed
2025-01-29 00:01:04
@article{9d152b41-fd9a-4052-b80a-07e23700c3d3,
  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.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.}},
  author       = {{Holmkvist, Petra and Roepstorff, K and Uronen-Hansson, Heli and Sandén, Caroline and Gudjonsson, Sigurdur and Hultman Patschan, Oliver and Grip, Olof and Marsal, Jan and Schmidtchen, Artur and Hornum, L and Erjefält, Jonas and Håkansson, K and Agace, William}},
  issn         = {{1933-0219}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{545--558}},
  publisher    = {{Elsevier}},
  series       = {{Mucosal Immunology}},
  title        = {{A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.}},
  url          = {{https://lup.lub.lu.se/search/files/2038540/5403468}},
  doi          = {{10.1038/mi.2014.87}},
  volume       = {{8}},
  year         = {{2015}},
}