Sa1773 Bromodomain Inhibition Enhances Tolerogenic Properties in Dendritic Cells; Application in Colitis

well described. We therefore focused our analysis of this phenomenon on NK cells. [Methods and Results] To further investigate these roles of NK cells, RAG-/and IL-7-/RAG-/mice that had received Naive T cells were depleted of NK cells using anti-asialo GM1 or antiNK1.1 antibodies. NK cell depletion at an early stage, but not at any later stage, during pathogenic effecter/memory T cell (TEM) development resulted in exacerbated colitis in recipient mice even in the absence of IL-7. The isolated NK cells derived from RAG-/and IL-7-/RAG-/mice indicated that the lack of IL-7 does not affect the differentiation and cellmediated cytotoxicity of NK cells either in vitro or in vivo. Increased CD44+ CD62LTEM and unique CD44CD62L(double negative, DN) T cell subsets were observed in the T cell-reconstituted RAG-/recipients when NK cells were depleted. The expressions of Fas, DR5, which are the specific receptors of Fas-L and TRAIL, respectively, and IL-7R in the DN T cell subset differed from that in TEM subset, indicating that the mechanism by which NK cells suppress the DN T cells is different from that by which they suppress the TEM cells, which is due to the apoptosis via Fas and/or DR5. [Conclusions] These results suggest that NK cells suppress colitis severity in the T cell-reconstituted recipient mice through targeting of CD4+ CD44+ CD62LTEM cells and, possibly, of the CD4+ CD44CD62Lsubset present at the early stage of pathogenic T cell development.