Expression of allergen in DC prevents pathology. or nontransgenic littermates (non-Tg) were sensitized with OVA 323-339 /alum (OVAp/alum; d0, d14), were sham-sensitized with PBS/alum (sham-sens), or were left unsensitized (un-sens) and . challenged with OVA (days 11–14 and 19–24 after sensitization). One day after the last . challenge, mice were euthanized for analysis. Lungs were collected and H&E ( A ) or periodic acid–Schiff (PAS) ( C ) stained, and images were analyzed to define cellular infiltrate ( B ) and mucus-filled goblet cell frequency (cells per 100 μm basement membrane) ( D ). Scale bars ( A and C ) depict 1 mm (low-power) and 200 μm (high-power inset). Data are representative micrographs from 4–6 mice per group pooled from 3 experiments or show values for individual mice pooled from 3 experiments, with box and whisker plots showing median, quartiles, and range. ANOVA/Tukey’s post-test
OT could not be induced in CCR9(-/-) or β7(-/-) mice, or when MAdCAM-1 was blocked in wild-type mice, indicating that gut-homing receptors are required for oral tolerization. Consistent with the role of all-trans retinoic acid in inducing gut-homing T cells, OT could not be induced in mice depleted of vitamin A. OT was rescued in CCR9(-/-) mice following adoptive transfer of wild-type T cells, but not CCR9(-/-) or β7(-/-) T cells. Gut-homing T cells are therefore necessary and sufficient to induce OT. Wild-type Treg and IL-10 were required to restore OT to CCR9(-/-) mice, indicating that homing and functional differentiation of IL-10-producing Treg in the gut is required for OT. Conversely, transfer of CCR9(-/-) or β7(-/-) T cells to wild-type mice partially inhibited OT.