Phenotypic changes and IDO over-expression in splenic dendritic cells after epicutaneous immunotherapy

RATIONALE: Epicutaneous immunotherapy (EPIT) was shown to induce Tregs expressing a variety of homing receptors, which are able to migrate and inhibit allergenic responses by antigen-presenting cells locally. This study aimed to characterize the effect of EPIT on splenic dendritic cells at the conclusion of immunotherapy and determine whether those changes are sustained.

METHODS: BALB/c mice were orally sensitized to peanut and treated with EPIT for 8 weeks or left untreated (Sham). Splenic dendritic cell subsets were characterized and activation of expression markers were analyzed by flow cytometry [MFI (median of fluorescence) for IDO, CD86, CD80 and MHC-II] immediately following treatment and 8 weeks after the end of the treatment.

RESULTS: Total splenic dendritic cells (CD11c⁺MHC-II⁺) exhibited higher MFI for IDO, MHC-II and CD80 following EPIT treatment compared to Sham (respectively 4632 vs 3565, 12978 vs 9447 (p˂0.05), 236.5 vs 212 (p˂0.01)). More specifically, only the resident CD11c⁺MHC-II⁺CD11b⁺CD8^- subset demonstrated over-expression of those molecules compared to Sham (IDO: 4548 vs 3543, CD80: 370.5 vs 353, MHC-II: 13881 vs 9624 (p˂0.05)). Increases in IDO and MHC-II expressions (p˂0.01) was sustained 8 weeks after the end of treatment in CD11c⁺MHC-II⁺ and CD11c⁺MHC-II⁺CD11b⁺CD8^-subsets (IDO MFI p˂0.01).

CONCLUSIONS: EPIT upregulated expression of IDO, CD80 and MHC-II in total splenic dendritic cells and resident CD11b⁺CD8^-, IDO over-expression being sustained for 8 weeks off treatment in both populations. EPIT seems to specifically modify the CD11b⁺ CD8^- subset, which might inhibit CD4⁺ proliferation by co-expression of IDO and MHC-II, and promote a tolerogenic environment.