Children with egg allergy have evidence of reduced neonatal CD4 +CD25 +CD127 lo/− regulatory T cell function

Abstract

The role of regulatory T (Treg) cells in allergic predisposition is not known. This study compared the frequency and function of cord blood Treg cells from nonallergic children (n = 18) with those from children who have egg allergy (n = 15) in the first year of life. CD4(+) effector T cells and autologous antigen-presenting cells isolated from cord blood mononuclear cells were cocultured with or without CD4(+)CD25(+)CD127(lo/-) Treg cells, and cytokine responses to staphylococcal endotoxin B were assessed after 48 hours. The addition of Treg cell populations to cord blood mononuclear cell cultures resulted in significant reduction in IL-10 (P = .002), IL-13 (P = .012), and IFN-gamma (P < .001) production. Consistent with other reports, effector CD4(+) T-cell responses (IFN-gamma and IL-13) tended to be lower in the allergic group. These neonates showed less significant Treg cell-associated suppression of IFN-gamma (P = .015) compared with that seen in the nonallergic group (P = .001). The allergic group was also less likely (44%) to show Treg cell-associated suppression of IFN-gamma effector responses compared with that seen in the nonallergic group (78%, P = .015). The magnitude of suppression (change in IFN-gamma level when CD4(+)CD25(+)CD127(lo/-) Treg cells were added to responding effector T-cell cultures) was significantly lower in the allergic group (P = .004). There were no between-group differences in the circulating CD4(+)CD25(+)CD127(lo/-) Treg cells (as a percentage of cord blood T cells) or in the FOXP3 expression of these cells. This study confirms the presence and activity of Treg cells in cord blood and provides preliminary evidence of differences in neonates who progress to allergic disease in the first year of life.