CD103- and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells

J Immunol. 2007 Jun 1;178(11):6861-6. doi: 10.4049/jimmunol.178.11.6861.

Abstract

Dendritic cells (DC) are able to capture, process, and present exogenous Ag to CD8(+) T lymphocytes through MHC class I, a process referred to as cross-presentation. In this study, we demonstrate that CD103(+) (CD11c(high)CD11b(low)) and CD103(-) (CD11c(int)CD11b(high)) DC residing in the lung-draining bronchial lymph node (brLN) have evolved to acquire opposing functions in presenting innocuous inhaled Ag. Thus, under tolerogenic conditions, CD103(-) DC are specialized in presenting innocuous Ag to CD4(+) T cells, whereas CD103(+) DC, which do not express CD8alpha, are specialized in presenting Ag exclusively to CD8(+) T cells. In CCR7-deficient but not in plt/plt mice, Ag-carrying CD103(+) DC are largely absent in the brLN, although CD103(+) DC are present in the lung of CCR7-deficient mice. As a consequence, adoptively transferred CD8(+) T cells can be activated under tolerizing conditions in plt/plt but not in CCR7-deficient mice. These data reveal that CD103(+) brLN DC are specialized in cross-presenting innocuous inhaled Ag in vivo. Because these cells are largely absent in CCR7(-/-) mice, our findings strongly suggest that brLN CD103(+) DC are lung-derived and that expression of CCR7 is required for their migration from the lung into its draining lymph node.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism*
  • Bronchi / cytology
  • Bronchi / immunology*
  • Bronchi / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cross-Priming / genetics
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Egg Proteins / administration & dosage
  • Egg Proteins / immunology
  • Egg Proteins / metabolism
  • Immunophenotyping
  • Integrin alpha Chains / biosynthesis
  • Integrin alpha Chains / metabolism*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Receptors, CCR7
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / deficiency
  • Receptors, Chemokine / genetics

Substances

  • Antigens, CD
  • Ccr7 protein, mouse
  • Egg Proteins
  • Integrin alpha Chains
  • OVA 323-339
  • OVA-8
  • Peptide Fragments
  • Receptors, CCR7
  • Receptors, Chemokine
  • alpha E integrins
  • Ovalbumin