title: Generation of experimental allergic airways inflammation in the absence of draining lymph nodes.
abstract: The objective of this study was to investigate the contribution of secondary lymphoid organs in the generation and maintenance of experimental allergic airway inflammation. We employed a previously reported murine model of respiratory mucosal allergic sensitization, induced by repeated aerosolizations of ovalbumin in the context of a GM-CSF airway environment. We executed this protocol in wild-type (WT) and lymphotoxin-alpha-deficient mice (LTalpha-KO) mice, which are devoid of lymph nodes (LNs) and possess rudimentary spleen structures. Despite the lack of pulmonary LNs draining the airway compartment, LTalpha-KO mice were fully capable of mounting a robust inflammatory response in the airways, consisting of Th2 polarized CD4+ T cells and eosinophils. This was accompanied by IL-5, IL-13, and IFN-gamma production by splenocytes and generation of ovalbumin-specific serum IgE. Exposure to the same antigen 7 weeks after complete resolution of airway inflammation once again induced a Th2 polarized infiltrate, demonstrating intact immunological memory. To investigate inherent plasticity in establishing antigen-specific immunity, mice were splenectomized before sensitization. Allergic sensitization was completely abrogated in splenectomized LTalpha-KO mice, compared with eusplenic LTalpha-KO controls. These data demonstrate that secondary lymphoid organs, either LN or spleen, are essential for the generation of allergic airway responses.
authors.affiliation: Department of Pathology and Molecular Medicine, and Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: B U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: D
authors.initials: D
authors.lastname: Alvarez
authors.forename: M
authors.initials: M
authors.lastname: Vidric
authors.forename: S
authors.initials: S
authors.lastname: Goncharova
authors.forename: M R
authors.initials: MR
authors.lastname: Stämpfli
authors.forename: A J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: J C
authors.initials: JC
authors.lastname: Gutierrez-Ramos
authors.forename: M
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007156:Immunologic Memory; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000002:abnormalities / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000633:toxicity; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000276:immunology*; D013156:Splenectomy; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D008233:Lymphotoxin-alpha; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin