Mapping of the lingual immune system reveals the presence of both regulatory and effector CD4+ T cells
- 13 November 2009
- journal article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 39 (12), 1910-1919
- https://doi.org/10.1111/j.1365-2222.2009.03337.x
Abstract
Sublingual immunotherapy (SLIT) is safe and reduces both symptoms and medication requirements in patients with type I respiratory allergies. Nonetheless, immune mechanisms underlying SLIT need to be further documented. A detailed characterization of the lingual immune system was undertaken in mice, to investigate the presence of tolerogenic and pro-inflammatory mechanisms. Immune cells were characterized in lingual tissues from BALB/c mice using immunohistology and flow cytometry. Resident CD4(+) T cells were sorted and toll-like receptor (TLR) expression profiles as well as functional characterization were assessed by RT-PCR, T cell suppressive assays and cytokine gene expression, respectively. Eosinophils and mast cells were only detected in submucosal tissues. No NK, NK-T, gamma/delta, CD8(+) T cells, nor B-lymphocytes were detected. Potential antigen presenting cells include various subsets of dendritic cells (CD207(+) Langerhans cells, CD11b(+)CD11c(+) myeloid cells and 120G8(+) plasmacytoid DCs) together with F4/80(+) macrophages. Noteworthy, both CD103(-) and CD103(+) CD4(+) T cells expressing TLR2 and TLR4 receptors are present along the lamina propria, in vicinity of myeloid CD11b(+)CD11c(+/-) dendritic cells. Such resident lingual CD4(+) T lymphocytes comprise both suppressive T cells as well as cells with memory/effector functions (i.e. expressing IFN gamma, IL4, IL10 and IL17 genes following stimulation), irrespective of the presence of the mucosal addressing marker CD103. The sublingual route is pertinent to induce antigen-specific tolerance, due to (i) limited numbers of pro-inflammatory cells, rather located in submucosal tissues, (ii) co-localization of APCs and resident CD4(+) T cells with regulatory functions. Since the oral immune system can also elicit pro-inflammatory effector responses, the cytokine milieu in which allergens are presented by sublingual APCs needs to be controlled during immunotherapy (e.g. with adjuvants) in order to favour tolerance over inflammation.Keywords
This publication has 45 references indexed in Scilit:
- Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasisThe Journal of Experimental Medicine, 2009
- Sublingual vaccination with influenza virus protects mice against lethal viral infectionProceedings of the National Academy of Sciences, 2008
- Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responsesNature Immunology, 2007
- IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma ModelInternational Archives of Allergy and Immunology, 2007
- Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary reportAnnals of Allergy, Asthma & Immunology, 2005
- Efficacy and safety of sublingual immunotherapyAnnals of Allergy, Asthma & Immunology, 2004
- Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4+CD25+ interleukin‐10+ T cells expressing peripheral tissue trafficking markersClinical and Experimental Allergy, 2004
- IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapyEuropean Journal of Immunology, 2003
- Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in VivoThe Journal of Experimental Medicine, 2001
- Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in VivoScience, 1990