Regulatory T Cells in Early Life: Comparative Study of CD4 ⁺CD25 ^high T Cells from Foals and Adult Horses

Abstract

The immune system of mammals is subject to continuous development during the postnatal phase of life. Studies following the longitudinal development of the immune system in healthy children are limited both by ethical considerations and sample volumes. Horses represent a particular valuable large animal model for T regulatory (Treg) cells and allergy research. We have recently characterised Treg cells from horses, demonstrated their regulatory capability and showed both their expansion and induction in vitro. Insect bite hypersensitivity (IBH) is a common allergy in horses resembling atopic dermatitis and studies have shown that first exposure to allergens in adult life results in an increased incidence of IBH. The aim of the present study was to characterize circulating CD4 ⁺CD25 ^highFoxP3 ⁺cells in foals, evaluate their suppressive capability and their in vitro induction compared to adult horses. 19 foals (age range, 1–5 months), their adult mothers and six one-year-old horses (yearlings) were included in the study. The proportion of FoxP3 ⁺ cells within the circulating CD4 ⁺CD25 ^high population was significantly higher in foals (47%) compared to their mothers (18%) and to yearlings (26%). Treg cells from foals also displayed a higher suppressive capability. Furthermore, CD4 ⁺CD25 ^high cells in foals could be induced in vitro from CD4 ⁺CD25 ⁻ cells in a significantly higher proportion compared to mares. These cells also displayed a significantly enhanced suppressive capability. In summary these findings support the notion that exposure of horses to allergens during maturation of the immune system assists the establishment of induced (i)Treg driven tolerance.