Antigen Concentration and Precursor Frequency Determine the Rate of CD8+ T Cell Tolerance to Peripherally Expressed Antigens

摘要: Expression of transgene-encoded proteins in the pancreatic islets can cause peripheral deletion T cells. However, tolerance has not been observed all transgenic models. It proposed that determining factor for successful is amount Ag cross-presented by quiescent APCs. Using InsHA mice, which demonstrate to influenza virus hemagglutinin (HA) expressed islet β cells, we have investigated consequences when different amounts HA are expressed. As compared with mice heterozygous transgene, homozygous demonstrated enhanced activation and proliferation K d -restricted HA-specific CD8 + cells lymph nodes. despite such activation, insulitis was observed, were gradually functionally deleted. Deletion these activated occurred much more rapidly than mice. These data there a direct correlation between periphery, both degree cell nodes rate This strongly supports hypothesis through cross-presentation Ags noninflammatory environment an important part normal mechanism islets.