CD4+CD25+ T cells regulate the intensity of hypersensitivity responses to peanut, but are not decisive in the induction of oral sensitization.
BACKGROUND
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a critical role in the maintenance of self-tolerance and it has been suggested that these Tregs may also be involved in preventing allergic disease.


OBJECTIVE
The precise role of CD4+CD25+ T cells in the regulation of allergic responses to mucosal antigens remains to be elucidated. In the present study, it was investigated whether CD4+CD25+ T cells are involved in the induction of oral tolerance and whether they play a role in controlling hypersensitivity responses to food proteins.


METHODS
CD4+CD25+ T cells were depleted with PC61 mAb before the induction of low dose oral tolerance to peanut extract (PE). In addition, CD4+CD25+ T cell depletion was performed during sensitization or before oral challenge, using a C3H/HeOuJ mouse model of allergic sensitization to peanut.


RESULTS
Oral tolerance to PE could not be induced in CD4+CD25+ T cell-depleted mice. However, CD4+CD25+ T cell depletion during long-term exposure to PE alone did not result in allergic sensitization. In sensitized mice, anti-CD25 treatment during oral exposure resulted in higher levels of PE-specific IgE and increased mast cell degranulation upon an oral challenge. In contrast, anti-CD25 treatment of PE-sensitized mice before oral challenges did not affect the level of mast cell degranulation.


CONCLUSIONS
These results indicate that CD4+CD25+ Tregs are involved in maintaining tolerance to oral antigens and regulate the intensity of an IgE-mediated food hypersensitivity response, but are not crucial in preventing sensitization. Accordingly, CD4+CD25+ Tregs may represent a potential tool for the treatment of food allergic disorders.
van Wijk
F
F
Wilhelmina Children's Hospital, Department of Pediatric Immunology, and Institute for Risk Assessment Sciences, Department of Immunotoxicology, Utrecht University, Utrecht, The Netherlands. F.vanWijk@umcutrecht.nl
Wehrens
E J M
EJ
Nierkens
S
S
Boon
L
L
Kasran
A
A
Pieters
R
R
Knippels
L M J
LM
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005260:Female; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology*; D010936:Plant Extracts / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D010936:Plant Extracts; D007073:Immunoglobulin E