Cathepsin B and D drive the fibrogenic potential of pancreatic stellate cells and modulate the stromal compartment in pancreatic ductal adenocarcinoma (PDAC)

TGFβ1 is considered to be required for peripheral maintenance of CD4+CD25+FOXP3+ Treg cells. However, we demonstrate no reduction in the percentage of such T cells in the spleens and thymi of Tgfb1−/− mice. Although putative Treg cells, characterized as CD4+CD25+FOXP3+CD62L+ T cells, are increased in Tgfb1−/− mice, they may be inadequate to control activated T cells since the ratio of activated T cells:putative Treg cells is several-fold higher in Tgfb1−/− mice than in control mice. We further show that whereas Tgfb1−/− mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in putative Treg cells, there are no detectable CD4+CD25+ T cells in the spleens of DO11.10 Rag1−/− mice suggesting that Treg-cell generation is self-antigen dependent regardless of whether they express Tgfb1. Finally, we demonstrate that Tgfb1−/− T cells remain responsive to the suppressive effect of TGFβ1 in vitro. These data suggest that TGFβ1 is required for the regulatory function of Treg cells to prevent activation of T cells and autoimmunity.