Anatomical Location Determines the Distribution and Function of Dendritic Cells and Other APCs in the Respiratory Tract

• Published in: The Journal of immunology (1950) Vol. 175; no. 3; pp. 1609 - 1618
• Main Authors: von Garnier, Christophe, Filgueira, Luis, Wikstrom, Matthew, Smith, Miranda, Thomas, Jennifer A, Strickland, Deborah H, Holt, Patrick G, Stumbles, Philip A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.08.2005
• Subjects: Amino Acid Sequence; Animals; Antigen Presentation - immunology; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - ultrastructure; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; CD11c Antigen - biosynthesis; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Cycle - immunology; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - ultrastructure; Female; Histocompatibility Antigens Class II - biosynthesis; Immunophenotyping; Lung - cytology; Lung - immunology; Lung - metabolism; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymph Nodes - metabolism; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Myeloid Cells - immunology; Myeloid Cells - metabolism; Respiratory Mucosa - cytology; Respiratory Mucosa - immunology; Respiratory Mucosa - ultrastructure; Resting Phase, Cell Cycle - immunology; Signal Transduction - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.3.1609

APCs, including dendritic cells (DC), are central to Ag surveillance in the respiratory tract (RT). Research in this area is dominated by mouse studies on purportedly representative RT-APC populations derived from whole-lung digests, comprising mainly parenchymal tissue. Our recent rat studies identified major functional differences between DC populations from airway mucosal vs parenchymal tissue, thus seriously questioning the validity of this approach. We addressed this issue for the first time in the mouse by separately characterizing RT-APC populations from these two different RT compartments. CD11c(high) myeloid DC (mDC) and B cells were common to both locations, whereas a short-lived CD11c(neg) mDC was unique to airway mucosa and long-lived CD11c(high) macrophage and rapid-turnover multipotential precursor populations were predominantly confined to the lung parenchyma. Airway mucosal mDC were more endocytic and presented peptide to naive CD4+ T cells more efficiently than their lung counterparts. However, mDC from neither site could present whole protein without further maturation in vitro, or following trafficking to lymph nodes in vivo, indicating a novel mechanism whereby RT-DC function is regulated at the level of protein processing but not peptide loading for naive T cell activation.