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CD103^– and CD103⁺ Bronchial Lymph Node Dendritic Cells Are Specialized in Presenting and Cross-Presenting Innocuous Antigen to CD4⁺ and CD8⁺ T Cells¹

Maria-Luisa del Rio^*, Jose-Ignacio Rodriguez-Barbosa^*, Elisabeth Kremmer and Reinhold Förster^2,*

^* Institute of Immunology, Hannover Medical School, Hannover, Germany; and Institute of Molecular Immunology, National Research Center, Munich, Germany

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^highCD11b^low) and CD103^– (CD11c^intCD11b^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 CD8, 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant SFB587-B3 from the German Research Foundation (to R.F.).

² Address correspondence and reprint requests to Dr. Reinhold Förster, Institute of Immunology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail address: foerster.reinhold{at}mh-hannover.de

³ Abbreviations used in this paper: DC, dendritic cell; BMDC, bone marrow-derived DC; LN, lymph node; brLN, bronchial LN; i.t., intratracheal(ly).

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