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Immature dendritic cells (DCs) sample tissue-specific antigens (TSAs) and process them for "crosspresentation" via major histocompatibility complex (MHC) class I and II 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 autoreactive 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.

Original publication




Journal article



Publication Date





521 - 532


Animals, Antigens, Apoptosis, Autoimmune Diseases, CD8-Positive T-Lymphocytes, Cell Line, Cross-Priming, Dendritic Cells, Immune Tolerance, Listeria monocytogenes, Lymphoid Tissue, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Ovalbumin, rac1 GTP-Binding Protein