Dendritic cell-nerve clusters are sites of T cell proliferation in allergic airway inflammation.
Interactions between T cells and dendritic cells in the airway mucosa precede secondary immune responses to inhaled antigen. The purpose of this study was to identify the anatomical locations where dendritic cell-T cell interactions occur, resulting in T cells activation by dendritic cells. In a mouse model of allergic airway inflammation, we applied whole-mount immunohistology and confocal microscopy to visualize dendritic cells and T cells together with nerves, epithelium, and smooth muscle in three dimensions. Proliferating T cells were identified by the detection of the incorporation of the nucleotide analogue 5-ethynyl-2'-deoxyuridine into the DNA. We developed a novel quantification method that enabled the accurate determination of cell-cell contacts in a semi-automated fashion. Dendritic cell-T cell interactions occurred beneath the smooth muscle layer, but not in the epithelium. Approximately 10% of the dendritic cells were contacted by nerves, and up to 4% of T cells formed clusters with these dendritic cells. T cells that were clustered with nerve-contacting dendritic cells proliferated only in the airways of mice with allergic inflammation but not in the airways of negative controls. Taken together, these results suggest that during the secondary immune response, sensory nerves influence dendritic cell-driven T cell activation in the airway mucosa.
Veres
Tibor Z
TZ
Dept. of Immunology, Allergology, and Immunotoxicology, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany.
Shevchenko
Marina
M
Krasteva
Gabriela
G
Spies
Emma
E
Prenzler
Frauke
F
Rochlitzer
Sabine
S
Tschernig
Thomas
T
Krug
Norbert
N
Kummer
Wolfgang
W
Braun
Armin
A
D000818:Animals; D039521:CD11c Antigen / Q000235:genetics; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin; D012137:Respiratory System / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure
D039521:CD11c Antigen; D010047:Ovalbumin