Allergen-responsive CD4+CD25+ Regulatory T Cells in Children who Have Outgrown Cow's Milk Allergy

Abstract

Cow's milk allergy in children is often of short duration, which makes this disorder an interesting clinical model for studies of tolerance to dietary antigens. Here, we studied T cell responses in 21 initially allergic children who, after a milk-free period of >2 mo, had cow's milk reintroduced to their diet. Children who outgrew their allergy (tolerant children) had higher frequencies of circulating CD4+CD25+ T cells and decreased in vitro proliferative responses to bovine β-lactoglobulin in peripheral blood mononuclear cells (PBMCs) compared with children who maintained clinically active allergy. No significant difference in proliferative activity stimulated by the polyclonal mitogen phytohemagglutinin was observed between the two groups. Depletion of CD25+ cells from PBMCs of tolerant children led to a fivefold increase in in vitro proliferation against β-lactoglobulin. This suggests that tolerance is associated with the appearance of circulating CD4+CD25+ regulatory T (Treg) cells that are capable of suppressing the effector T cells generated 1 wk after reintroduction of cow's milk. The suppressive function of the CD4+CD25+ Treg cells was shown to be partly cell contact dependent. Collectively, our study provides human data to suggest that mucosal induction of tolerance against dietary antigens is associated with the development of CD4+CD25+ Treg cells.

Food Allergy and the Oral Immunotherapy Approach

“…The balance of effector and Treg cells in the gut appears to regulate the tolerance to food allergens. So, the failure to induced Treg (iTreg) cells at the lamina propria is implicated in the development of food allergies (Karlsson et al 2004;Shreffler et al 2009). Treg cells are characterized by the expression of the forkhead transcription factor FoxP3.…”

Cloning, Expression, and Mapping of Allergenic Determinants of αS1-Casein, a Major Cow’s Milk Allergen

“…Unlike in respiratory allergy, which proceeds untreated from mild (e.g., rhinoconjunctivitis) to severe manifestations (e.g., asthma), many milk-allergic children grow out their allergy, and the induction of tolerance against cow's milk allergens has already been described (10,11). In this context it has been reported that allergen-specific CD4 ϩ CD25 ϩ regulatory T cells may be involved in the induction of tolerance against cow's milk allergens in children who outgrew cow's milk allergy (12).…”

Intestinal Microbiocenosis, Food Tolerance and Food Allergy. Current State of a Problem

“…Клетки популяции CD4+CD25+Treg подавляют реак-ции на пищевые антигены, однако в раннем возрасте могут возникнуть трудности при вовлечении этих клеток в качестве основных медиаторов подавления Т клеток слизистой оболочки, поскольку большое число Т клеток в раннем грудном возрасте не имеет определенного фенотипа. Большой интерес представляют также результаты исследования, в котором показано, что у младенцев, сенсибилизированных к белкам коровьего молока и раз-вивших толерантность к возрасту 2-3 лет, отмечалось увеличение числа регуляторных популяций лимфоцитов -CD4+ CD25+ клеток [35]. Все эти данные подтверждают, что кишечные эпителиальные клетки вовлечены в раз-витие толерогенных дендритных клеток и Т-регуляторных клеток, которые занимают центральное место в индукции оральной толерантности.…”