Anatomical location determines the distribution and function of dendritic cells and other APCs in the respiratory tract.
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.
von Garnier
Christophe
C
Division of Cell Biology, Telethon Institute for Child Health Research, Centre for Child Health Research and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. christophe@ichr.uwa.edu.au
Filgueira
Luis
L
Wikstrom
Matthew
M
Smith
Miranda
M
Thomas
Jennifer A
JA
Strickland
Deborah H
DH
Holt
Patrick G
PG
Stumbles
Philip A
PA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen