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

Journal article

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.

Authors: Luckashenak, N; Schroeder, S; Endt, K; Schmidt, D; Mahnke, K

• Journal: Immunity
• Volume: 28
• Issue: 4
• Pages: 521-532
• Publication date: 2008-04-01
• DOI: 10.1016/j.immuni.2008.02.018
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Apoptosis; Cross-Priming; Antigens; Lymphoid Tissue; Mice; Ovalbumin; Animals; Autoimmune Diseases; Cell Line; Mice, Inbred C57BL; Listeria monocytogenes; CD8-Positive T-Lymphocytes; rac1 GTP-Binding Protein; Immune Tolerance; Dendritic Cells; Mice, Transgenic; Mice, Knockout