title: Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node.
abstract: The major histocompatibility complex (MHC)-dependent presentation of processed tissue-specific self-antigens can contribute to either peripheral (extrathymic) tolerance or the differentiation of autoreactive T cells. Here, we have studied the MHC class II molecule presentation of gastric parietal cell (PC)-specific H(+)/K(+)-ATPase, which induces a destructive autoimmune gastritis in BALB/c mice lacking CD4(+) CD25(+) regulatory T cells. Immunofluorescence microscopy showed physical association of CD11c(+) dendritic cells (DCs) with PCs in the gastric mucosa. H(+)/K(+)-ATPase protein was found within vesicular compartments of a few CD11c(+) DCs only in the draining gastric lymph node (LN) and these antigen-containing DCs increased markedly in number with the onset of tissue destruction in autoimmune animals. Both CD8alpha(hi) and CD8alpha(lo) gastric DCs, but not peripheral or mesenteric DCs, showed evidence of constitutive in vivo processing and presentation of H(+)/K(+)-ATPase. These data provide direct support for a widely held model of local tissue antigen uptake and trafficking by DCs in normal animals and demonstrate that DCs in the draining LN can present a tissue-specific self-antigen under noninflammatory conditions without fully deleting autoreactive T cells or inducing active autoimmunity.
authors.affiliation: Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Clemens
authors.initials: C
authors.lastname: Scheinecker
authors.forename: Rebecca
authors.initials: R
authors.lastname: McHugh
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic
chemical_list: D001324:Autoantigens; D017506:H(+)-K(+)-Exchanging ATPase