Oral tolerance inhibits DTH in the sensitization phase by Treg-mediated suppression of DC functions in skin dLNs

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1012
Abstract ID: 4848

Presenting Author:
Arisa Akagi , Oral tolerance at Kyoto Univ.

Abstract:

Antigen (Ag)-specific skin immune responses such as delayed-type hypersensitivity (DTH) are suppressed by prior oral administration of Ag, depending on the induction of regulatory T cells (Tregs) in gut-draining lymph nodes (dLNs). Here, we aimed to clarify the exact phase and location where Tregs induced in gut-dLNs suppress DTH.

Prefeeding ovalbumin (OVA) attenuated DTH against OVA, consistent with previous studies. This attenuation was abrogated by in vivo depletion of Tregs. DTH responses elicited in OVA-fed and unfed mice, subsequent to the transfer of cells from dLNs of OVA-immunized skin, were comparable. In contrast, DTH responses were significantly attenuated in mice transferred with cells from dLNs of OVA-immunized skin in OVA-fed mice, suggesting that OVA-feeding inhibited the responses in the sensitization phase of DTH. Next, we assessed the capacity of DCs isolated from dLNs of OVA-immunized skin to prime OT-II T cells. OVA feeding did not affect T-cell priming capacity of DCs at 24 h post-immunization (d1), but impaired it at 48 h (d2). In vivo DC migration assay revealed OVA feeding did not affect the migration of Ag-bearing (Ag⁺) DCs to the dLNs. Expression levels of CD80 and CD86 on Ag⁺ DCs in tolerized mice were comparable to non-tolerized mice at d1 but lower at d2.

In conclusion, our data suggest that DTH responses in orally tolerized mice are inhibited in the sensitization phase via Treg-mediated suppression of DC functions in the skin-dLNs.