In vitro induction of functional allergen-specific CD4+ CD25high Treg cells in horses affected with insect bite hypersensitivity

Hamza, Eman; Akdis, C. A.; Wagner, B.; Steinbach, F.; Marti, Eliane Isabelle (2013). In vitro induction of functional allergen-specific CD4+ CD25high Treg cells in horses affected with insect bite hypersensitivity. Clinical and experimental allergy, 43(8), pp. 889-901. Blackwell Scientific Publications 10.1111/cea.12131

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BACKGROUND Insect bite hypersensitivity (IBH) is a recurrent allergic dermatitis of horses with similarities to human atopic eczema, caused by bites of insects of the genus Culicoides. Previous studies suggested a dysregulated T cell tolerance to Culicoides allergen in IBH-affected horses. OBJECTIVE We have investigated whether the suppressive function of CD4(+) CD25(high) cells is impaired in IBH-affected horses and possible ways to restore it. METHODS CD4(+) CD25(-) cells sorted from peripheral blood mononuclear cells (PBMC) were stimulated with irradiated autologous PBMC pulsed with Culicoides or tetanus toxoid as control antigen, in the presence of CD4(+) CD25(high) cells. Furthermore, Culicoides-specific CD4(+) CD25(high) regulatory cells were expanded or induced from CD4(+) CD25(-) cells in vitro in the presence of a combination of rIL-2 and rTGF-β1 (rIL-2/rTGF-β1) or of retinoic acid and rapamycin (RetA/Rapa). Proliferation was determined by [(3) H] thymidine incorporation and cytokine production measured by flow cytometry. RESULTS The ability of Culicoides- but not tetanus-stimulated CD4(+) CD25(high) cells to suppress proliferation of CD4(+) CD25(-) cells was significantly lower in IBH-affected horses (28%) than in healthy controls (86%). The decreased suppression in IBH-affected horses was associated with a significantly higher proportion of IL-4(+) cells and a lower percentage of FoxP3(+) IL-10(+) compared to controls. Addition of rIL-2/rTGF-β1 or of RetA/Rapa to Culicoides-stimulated CD4(+) CD25(high) cells from IBH-affected horses significantly increased the proportion of FoxP3(+) IL-10(+) cells. We also found that RetA/Rapa induced a more significant decrease in the frequency of IL-4(+) cells than rIL-2/rTGF-β1. Moreover, the suppressive activity of Culicoides-stimulated CD4(+) CD25(high) cells was significantly restored by both rIL-2/rTGF-β1and RetA/Rapa, albeit in an antigen-unspecific manner. In contrast, in vitro induced Culicoides-specific CD4(+) CD25(high) cells suppressed proliferation of CD4(+) CD25(-) cells in an antigen-specific manner. CONCLUSION AND CLINICAL RELEVANCE The in vitro induction of functional allergen-specific Treg cells in IBH-affected horses suggests a potential therapeutic use of these cells in allergy.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Hamza, Eman and Marti, Eliane Isabelle

Subjects:

600 Technology > 630 Agriculture

ISSN:

0954-7894

Publisher:

Blackwell Scientific Publications

Language:

English

Submitter:

Susanne Portner

Date Deposited:

22 Aug 2014 14:48

Last Modified:

14 Oct 2015 11:32

Publisher DOI:

10.1111/cea.12131

PubMed ID:

23889243

Uncontrolled Keywords:

allergy, CD4+ CD25+ T cells, FoxP3, IBH, Icelandic horses, IL-10, IL-4, retinoic acid and rapamycin, rIL-2 and rTGF-β1., Treg expansion, Treg induction, Treg suppression

BORIS DOI:

10.7892/boris.44044

URI:

https://boris.unibe.ch/id/eprint/44044

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