Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo

Immature dendritic cells (DCs) sample tissue-specific antigens (TSAs) and process them for cross-presentation via major histocompatibility complex (MHC) class I and 11 molecules. Findings with adoptively transferred T cell receptor (TCR)-transgenic CD8(+) T cells in transgenic mice expressing model TSA indicate that this process contributes to tolerance induction of CD8+ T cells, a phenomenon termed crosstolerance. However, up to now it has been unknown whether crosstolerance can also control autoimmune T cells specific for physiological nontransgenic TSA. Here, we showed that a DC-specific deficiency in uptake of apoptotic material inhibits crosspresentation in vivo. This defect allowed the accumulation of fully functional auto-reactive CD8+ T cells that could be activated for autoimmune attack in peripheral lymphoid organs. Thus, our data demonstrate the importance of crosstolerance induction by DCs as a vital instrument for controlling self-reactive T cells from the peripheral repertoire and preventing autoimmune disease.