The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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Published 21 October 2002. doi:10.1084/jem.20020991
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© Rockefeller University Press, 0022-1007/2002/10/1079 $5.00
The Journal of Experimental Medicine, Volume 196, Number 8, 1079-1090

Constitutive Presentation of a Natural Tissue Autoantigen Exclusively by Dendritic Cells in the Draining Lymph Node

Clemens Scheinecker1, Rebecca McHugh2, Ethan M. Shevach2 and Ronald N. Germain1

1 Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
2 Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892

Address correspondence to Ronald N. Germain, Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC-1892, Building 10, Room 11N311, Bethesda, MD 20892. Phone: 301-496-1904; Fax: 301-496-0222; E-mail: rgermain{at}nih.gov

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 CD8{alpha}hi and CD8{alpha}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.

Key Words: antigen-presenting cells • autoimmune disease • gastritis • autoantigen • CD11c antigen


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