title: Intraepithelial T-cell cytotoxicity, induced bronchus-associated lymphoid tissue, and proliferation of pneumocytes in experimental mouse models of influenza.
abstract: Immunopathologic examination of the lungs of mice with experimental influenza virus infection reveals three prominent findings. (i) There is rapidly developing perivascular (arterial) and peribronchial infiltration with T-cells and invasion of T-cells into the bronchiolar epithelium, separation of epithelial cells from each other and from the basement membrane, leading to defoliation of the bronchial epithelium. This reaction is analogous to a viral exanthema of the skin, such as measles and smallpox. This previously described but unappreciated reaction most likely is an effective way to eliminate virus-infected cells, but may contribute to acute toxicity and mortality. (ii) After this, there is formation of dense collections of lymphocytes adjacent to bronchi consisting mainly of B-cells, with a scattering of T-cells and macrophages. This is known as induced bronchial-associated lymphoid tissue (iBALT) and correlates with increased interleukin (IL)-17 in the lung. iBALT provides sites for a local immune reaction in the lung to both the original infection and related viral infections (heterologous immunity). (iii) Within the first 2-3 weeks, there is proliferation of type II pneumocytes and/or terminal bronchial epithelial cells extending from the terminal bronchioles into the adjacent alveoli, eventually leading to large zones of the lung filled with tumor-like epithelial cells with squamous metaplasia. The proliferation correlates with IL-17 and IL-22 expression, and the extent of this reaction appears to be determined by the availability of T-regulatory cells.
authors.affiliation: 1 New York State Department of Health, Wadsworth Center , Albany, New York.
authors.forename: Stewart
authors.initials: S
authors.lastname: Sell
authors.forename: Ian
authors.initials: I
authors.lastname: Guest
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
authors.forename: Erik
authors.initials: E
authors.lastname: Brincks
authors.forename: Mike
authors.initials: M
authors.lastname: Tighe
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blackman
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Richard W
authors.initials: RW
authors.lastname: Dutton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
mesh_terms: D056809:Alveolar Epithelial Cells / Q000502:physiology*; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*