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 "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.
Luckashenak
Nancy
N
Institute for Immunology, Ludwig-Maximilian-University, 80336 Munich, Germany.
Schroeder
Samira
S
Endt
Katrin
K
Schmidt
Darja
D
Mahnke
Karsten
K
Bachmann
Martin F
MF
Marconi
Peggy
P
Deeg
Cornelia A
CA
Brocker
Thomas
T
D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D002460:Cell Line; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D000941:Antigens; C107953:RAC1 protein, human; D010047:Ovalbumin; D020830:rac1 GTP-Binding Protein