The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens.
We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow-derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8alpha(+) dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced beta-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c(+)CD8alpha(+) cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8alpha(+) DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.
Belz
Gabrielle T
GT
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia. belz@wehi.edu.au
Behrens
Georg M N
GM
Smith
Chris M
CM
Miller
Jacques F A P
JF
Jones
Claerwen
C
Lejon
Kristina
K
Fathman
C Garrison
CG
Mueller
Scott N
SN
Shortman
Ken
K
Carbone
Francis R
FR
Heath
William R
WR
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D007108:Immune Tolerance; D016130:Immunophenotyping; D007328:Insulin / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats
D015703:Antigens, CD; D001426:Bacterial Proteins; D017931:DNA Primers; D007328:Insulin; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria