CD4+CD25+ T cells expressing FoxP3 in Icelandic horses affected with insect bite hypersensitivity.
Abstract: Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis caused by bites of midges from the genus Culicoides. We have shown previously that peripheral blood mononuclear cells (PBMC) from IBH-affected horses produce higher levels of IL-4 and lower levels of IL-10 and TGF-β1 than those from healthy horses, suggesting that IBH is associated with a reduced regulatory immune response. FoxP3 is a crucial marker of regulatory T cells (Tregs). Here we have determined the proportion of CD4(+)CD25(+)FoxP3(+) T cells by flow cytometry in PBMC directly after isolation or after stimulation with Culicoides extract or a control antigen (Tetanus Toxoid). There were no differences between healthy and IBH horses either in the proportion of FoxP3(+)CD4(+)CD25(+) cells in freshly isolated PBMC or in the following stimulation with Tetanus Toxoid. However, upon stimulation of PBMC with the allergen, expression of FoxP3 by CD4(+)CD25(+high) and CD4(+)CD25(+dim) cells was significantly higher in healthy than in IBH horses. Addition of recombinant IL-4 to PBMC from healthy horses stimulated with the allergen significantly decreased the proportion of FoxP3 expressing cells within CD4(+)CD25(+high). These results suggest that IBH is associated with a decreased number of allergen-induced Tregs. This could be a consequence of the increased IL-4 production by PBMC of IBH-affected horses.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication Date: 2011-06-06 PubMed ID: 21700344DOI: 10.1016/j.vetimm.2011.05.033Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study focused on the immune response of Icelandic horses affected by Insect Bite Hypersensitivity (IBH), discovering a diminished number of allergen-induced regulatory T cells (Tregs), possibly caused by increased IL-4 production in these horses.
Research Context and Goals
- The research looked into insect bite hypersensitivity (IBH), a condition in horses triggered by bites from midges, insects from the Culicoides genus. This ailment is characterized by a form of dermatitis mediated by the IgE antibody.
- Previous studies indicated that horses affected by IBH tend to have an abnormal immune response, producing higher levels of IL-4 and lower levels of IL-10 and TGF-β1 than those from healthy horses. This suggested that IBH is associated with a reduced regulatory immune response.
- One of the research objectives was to investigate this further by examining the expression of FoxP3, a crucial marker of Tregs (regulatory T cells), in CD4(+)CD25(+) T cells in horses.
Methodology and Observations
- The researchers examined the distribution of CD4(+)CD25(+)FoxP3(+) T cells in peripheral blood mononuclear cells (PBMC) right after isolation and after inducing them with Culicoides extract or a control antigen (Tetanus Toxoid).
- It was observed that there was no significant difference between the proportion of FoxP3(+)CD4(+)CD25(+) cells in freshly isolated PBMCs of healthy and IBH-affected horses, or after stimulation with Tetanus Toxoid.
- However, when the PBMCs were stimulated with allergen, the expression of FoxP3 in both CD4(+)CD25(+high) and CD4(+)CD25(+dim) cells was significantly higher in the healthy horses compared to the IBH-affected ones.
Conclusions and Implications
- This indicated that there was an association of IBH with a reduced number of allergen-induced Tregs which could potentially be linked to the increased IL-4 production in PBMC of IBH-affected horses.
- This result was confirmed when an addition of recombinant IL-4 to the PBMC in healthy horses, following allergen stimulation, led to a significant decrease in the proportion of FoxP3 expressing cells within CD4(+)CD25(+high).
- The research made significant strides in understanding the immune responses associated with IBH, potentially opening up new avenues for intervention and treatment strategies for the condition.
Cite This Article
APA
Hamza E, Steinbach F, Marti E.
(2011).
CD4+CD25+ T cells expressing FoxP3 in Icelandic horses affected with insect bite hypersensitivity.
Vet Immunol Immunopathol, 148(1-2), 139-144.
https://doi.org/10.1016/j.vetimm.2011.05.033 Publication
Researcher Affiliations
- Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland. eman.hamza@vetsuisse.unibe.ch
MeSH Terms
- Animals
- Cells, Cultured
- Ceratopogonidae / immunology
- Flow Cytometry / veterinary
- Forkhead Transcription Factors / biosynthesis
- Forkhead Transcription Factors / immunology
- Horse Diseases / immunology
- Horses
- Hypersensitivity / immunology
- Hypersensitivity / veterinary
- Insect Bites and Stings / immunology
- Insect Bites and Stings / veterinary
- Leukocytes, Mononuclear / immunology
- T-Lymphocytes, Regulatory / cytology
- T-Lymphocytes, Regulatory / immunology
Citations
This article has been cited 9 times.- Larson EM, Babasyan S, Wagner B. Phenotype and function of IgE-binding monocytes in equine Culicoides hypersensitivity. PLoS One 2020;15(5):e0233537.
- Jonsdottir S, Fettelschoss V, Olomski F, Talker SC, Mirkovitch J, Rhiner T, Birkmann K, Thoms F, Wagner B, Bachmann MF, Kündig TM, Marti E, Fettelschoss-Gabriel A. Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses. Vaccines (Basel) 2020 May 9;8(2).
- Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Immun Inflamm Dis 2019 Sep;7(3):130-149.
- Torsteinsdottir S, Scheidegger S, Baselgia S, Jonsdottir S, Svansson V, Björnsdottir S, Marti E. A prospective study on insect bite hypersensitivity in horses exported from Iceland into Switzerland. Acta Vet Scand 2018 Nov 3;60(1):69.
- Meulenbroeks C, van der Lugt JJ, van der Meide NM, Willemse T, Rutten VP, Zaiss DM. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity. PLoS One 2015;10(4):e0122090.
- Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, Walker NJ, Clark KC, Watson JL, Borjesson DL. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses. Stem Cell Res Ther 2015 Apr 15;6(1):73.
- Hamza E, Mirkovitch J, Steinbach F, Marti E. Regulatory T cells in early life: comparative study of CD4+CD25high T cells from foals and adult horses. PLoS One 2015;10(3):e0120661.
- Junginger J, Schwittlick U, Lemensieck F, Nolte I, Hewicker-Trautwein M. Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs. Vet Res 2012 Mar 22;43(1):23.
- Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med 2012 May-Jun;26(3):457-82.
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