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Long-Term Deposition of Inhaled Antigen in Lung Resident CD11b^–CD11c⁺ Cells

Malaghan Institute of Medical Research, Wellington, New Zealand; Department of Dermatology, DIAID, and Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria; and INSERM U503-IFR128, Lyon, France

Correspondence and requests for reprints should be addressed to Dr. Franca Ronchese, Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand. E-mail: fronchese{at}malaghan.org.nz

In this study we report the characterization of a population of lung resident CD11b^–CD11c⁺ cells that are able to take up inhaled antigen and retain it for extended periods of time. Ovalbumin conjugated to fluorescein-isothiocyanate (FITC-OVA) administered intranasally to mice was taken up by two main populations of cells in the lung, a migratory CD11c⁺CD11b⁺ population consisting of dendritic cells (DC), which rapidly transported antigen to the draining lymph node (LN), and a resident CD11b^–CD11c⁺ population that retained engulfed antigen without apparently degrading it for up to 8 wk after administration. The FITC⁺CD11b^–CD11c⁺ cells did not migrate to draining LN at a detectable rate, and did not up-regulate expression of costimulatory molecules in response to LPS treatment. FITC⁺CD11b^–CD11c⁺ cells were found in the lung and bronchoalveolar lavage fluid, and their distribution was compatible with macrophages. Although FITC⁺CD11b^–CD11c⁺ cells expressed the DC marker DEC205 and other molecules associated with antigen-presenting cell function, they did not induce proliferation of antigen-specific CD4⁺ T cells in vitro or acute cytokine production by activated CD4⁺ T cells in vivo. Thus, FITC⁺CD11b^–CD11c⁺ cells appear to represent an intermediate cell type sharing properties with DC and macrophages. These cells may have a role in modulating the responses of lung resident T cells to inhaled antigens.

Key Words: animal models • antigen presentation/processing • lung inflammation

CLINICAL RELEVANCE This article reports the characterization of a population of lung cells that take up inhaled antigen and retain it for several weeks. Retention of antigen by these cells had not been reported before, and may have important implications for immune responses in the lung.

 

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