Dysfunction of hepatic regulatory T cells in experimental sclerosing cholangitis is associated with IL-12 signaling

In this study we successfully enriched regulatory T cells (Treg) in the liver using injections with IL-2/IL-2ab complex. Enriched Treg were mainly located in areas of inflammation, but they had no impact on liver inflammation or fibrosis in two different cholangitis mouse models. We found that liver derived Treg had less suppressive capacity compared to splenic derived Treg. We used microarray analysis of IL-2/IL-2ab complex enriched liver and splenic derived regulatory T cells in order to elucidate the organ specific differences. We identified upregulation of IL12 receptor beta 2 on hepatic Treg and could identify IL-12 signalling as key factor for reduced suppressive capacity of regulatory T cells. Regulatory T cells were expanded by repeated injection of IL-2/IL-2Ab complex in vivo. Enriched Treg were isolated from spleen and liver for RNA extraction and hybridization on Affymetrix microarrays.