Abstracts (complete list) - Wissenschaft Online

Diana Fleissner, Jan Buer, Astrid Westendorf
Impact of intestinal dendritic cells for the induction of
tolerance or pathology
Several studies have suggested that chronic inflammatory bowel disease may be a
consequence of antigen specific recognition by appropriate T cells which expand and
induce immunopathology. To analyse the impact of intestinal dendritic cells (DCs) for
the presentation of intestinal self-antigens and the induction of immunopathology or
tolerance we used VILLIN-HA transgenic mice that show specific expression of
hemagglutinin (HA) from influenza virus A exclusively in enterocytes of the intestinal
epithelium. Adoptive transfer of naïve HA-specific CD8+ T cells into VILLIN-HA recipient
mice leads to strong expansion of antigen-specific CD8+ T cells and the development of
severe intestinal inflammation. In contrast, adoptive transfer of HA-specific CD4+ T
cells into VILLIN-HA transgenic mice results in proliferation of HA-specific T cells but
fails to induce intestinal inflammation. Interestingly, cotransfer of HA-specific CD4+ and
CD8+ T cells further aggravates the pathology. Therefore, auto-reactive CD8+ T cells
may come first before pathogenic CD4+ T cells ultimately drive disease. Based on these
findings we analyzed the impact of intestinal DCs for the presentation of intestinal selfantigen.
Comparison of DCs from the mesenteric lymphnode (MLN) versus lamina
propria (LP) reveals a slight upregulation of MHC class II, CD80 and CD86 on DCs
isolated from the LP. Furthermore, DCs isolated from the MLN of VILLIN-HA transgenic
induce proliferation of HA-specific CD8+ and CD4+ T cells without adding of external HA
peptide in vitro. These results demonstrate that DCs sample intestinal epithelial
antigens in the lamina propria and migrate to the MLN where they present the antigen.
In future experiments we want to characterize the phenotype of DC-stimulated CD8+
and CD4+ T cells in more detail to dissect the pathologic and regulatory function of
these cells. In conclusion, the gut-associated mucosal immune system develops certain
mechanisms which lead either to immunity or tolerance.