CD4(+) CD25(+) T regulatory cells do not transfer oral tolerance to peanut allergens in a mouse model of peanut allergy.
Clin Exp Allergy
; 41(9): 1324-33, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21338425
ABSTRACT
BACKGROUND:
Recent studies have implicated CD4(+) CD25(+) regulatory T cells (nTregs) in the maintenance of tolerance to oral antigens and in the regulation of the food allergic IgE response.OBJECTIVE:
The objective was to assess if nTregs can transfer allergen-specific oral tolerance to naïve, non-TCR transgenic mice and regulate peanut extract (PE)-specific hypersensitivity responses. Additionally, the role of the regulatory cytokines IL-10 and TGF-ß in the modulation of peanut-allergic sensitization was studied.METHODS:
CD25-enriched T cells from PE-tolerant mice were adoptively transferred to recipient mice, which were subsequently sensitized to PE. Depletion of CD25(+) cells and neutralization of IL-10 and TGF-ß were compared in a CH3/HeOuJ mouse model of peanut-allergic sensitization.RESULTS:
Transfer of CD25(+) Tregs-enriched cell populations did not affect the PE-specific cytokine production or PE-specific antibody levels compared with control mice but interestingly resulted in a decrease of mast cell responsiveness. On the contrary, transfer of CD25(+) Tregs-depleted cells caused an increase in non-specific cytokine production, in the absence of changes in PE-specific responses. TGF-ß neutralization resulted even in a larger increase in spontaneous release of all cytokines measured (IL-4, IL-5, IL-10, IL-13, and IFN-γ), but surprisingly also to a higher PE-specific Th2-associated (IL-4, IL-5, IL-13) cytokine production compared with depletion of CD25 cells or neutralization of IL-10. Similarly, depletion of CD25 cells and TGF-ß neutralization but not of IL-10 neutralization lead to an increase in PE-specific antibody levels and elevated mast cell degranulation following a PE challenge. CONCLUSIONS AND CLINICAL RELEVANCE We conclude that CD4(+) CD25(+) Tregs from non-transgenic-tolerant mice cannot transfer specific oral tolerance of exogenous antigens to naïve mice and are more involved in general immune suppressive mechanisms. However, we found evidence that TGF-ß secreting Tregs (Th3) may play an important role.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arachis
/
Alérgenos
/
Linfocitos T Reguladores
/
Hipersensibilidad al Cacahuete
/
Tolerancia Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos