Generation of experimental allergic airways inflammation in the absence of draining lymph nodes

• Published in: The Journal of clinical investigation 2001-08, Vol.108 (4), p.577-583
• Main Authors: Gajewska, B U, Alvarez, D, Vidric, M, Goncharova, S, Stämpfli, M R, Coyle, A J, Gutierrez-Ramos, J C, Jordana, M
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Bronchoalveolar Lavage Fluid; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Disease Models, Animal; Eosinophils - immunology; Genetic Vectors - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Immunoglobulin E - biosynthesis; Immunologic Memory; Inflammation; Interferon-gamma - biosynthesis; Interleukin-13 - biosynthesis; Interleukin-5 - biosynthesis; Lymph Nodes - abnormalities; Lymph Nodes - immunology; Lymphotoxin-alpha - genetics; Lymphotoxin-alpha - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - toxicity; Pulmonary Eosinophilia - etiology; Pulmonary Eosinophilia - immunology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - physiology; Respiratory Hypersensitivity - etiology; Respiratory Hypersensitivity - immunology; Specific Pathogen-Free Organisms; Spleen - abnormalities; Spleen - cytology; Spleen - immunology; Splenectomy; Th2 Cells - immunology
• ISSN: 0021-9738
• DOI: 10.1172/jci200112627

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.