Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1016/j.immuni.2008.02.018

Type

Journal article

Journal

Immunity

Publication Date

04/2008

Volume

28

Pages

521 - 532

Keywords

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