Journal Article

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

Gudjonsson, S, Roepstorff, K, Agace, W W, Marsal, J, Patschan, O, Erjefält, J S, Holmkvist, P, Grip, O, Håkansson, K, Sandén, C, Uronen-Hansson, H, Hornum, L, Schmidtchen, A

2015

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/554/1898 / 631/250/262 / 631/250/347 / Allergology / Antibodies / Basic Medicine / Biomedical and Life Sciences / Biomedicine / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - pathology / Crohn Disease - genetics / Crohn Disease - immunology / Crohn Disease - pathology / Epithelial Cells - immunology / Epithelial Cells - pathology / Gastroenterology / Gene Expression Regulation / Granulocyte-Macrophage Colony-Stimulating Factor - genetics / Granulocyte-Macrophage Colony-Stimulating Factor - immunology / Humans / Immunity, Innate / Immunity, Mucosal / Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi) / Immunologic Memory / Immunology / Immunology in the Medical Area (including Cell and Immunotherapy) / Interferon-gamma - genetics / Interferon-gamma - immunology / Interleukin-13 - genetics / Interleukin-13 - immunology / Interleukin-15 - genetics / Interleukin-15 - immunology / Interleukin-22 / Interleukin-5 - genetics / Interleukin-5 - immunology / Interleukin-6 - genetics / Interleukin-6 - immunology / Interleukins - genetics / Interleukins - immunology / Intestinal Mucosa - immunology / Intestinal Mucosa - pathology / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / Nasal Polyps - genetics / Nasal Polyps - immunology / Nasal Polyps - pathology / Primary Cell Culture / Receptors, Interleukin-18 - genetics / Receptors, Interleukin-18 - immunology / Receptors, Tumor Necrosis Factor, Member 25 - genetics / Receptors, Tumor Necrosis Factor, Member 25 - immunology / Signal Transduction / Skin - cytology / Skin - immunology / Tumor Necrosis Factor Ligand Superfamily Member 15 - genetics / Tumor Necrosis Factor Ligand Superfamily Member 15 - immunology / Tumor Necrosis Factor-alpha - genetics / Tumor Necrosis Factor-alpha - immunology