Generation of experimental allergic airways inflammation in the absence of draining lymph nodes
Beata U. Gajewska, … , José-Carlos Gutierrez-Ramos, Manel Jordana
Beata U. Gajewska, … , José-Carlos Gutierrez-Ramos, Manel Jordana
Published August 15, 2001
Citation Information: J Clin Invest. 2001;108(4):577-583. https://doi.org/10.1172/JCI12627.
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Article

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-α–deficient mice (LTα-KO) mice, which are devoid of lymph nodes (LNs) and possess rudimentary spleen structures. Despite the lack of pulmonary LNs draining the airway compartment, LTα-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-γ 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 LTα-KO mice, compared with eusplenic LTα-KO controls. These data demonstrate that secondary lymphoid organs, either LN or spleen, are essential for the generation of allergic airway responses.

Authors

Beata U. Gajewska, David Alvarez, Mariana Vidric, Susanna Goncharova, Martin R. Stämpfli, Anthony J. Coyle, José-Carlos Gutierrez-Ramos, Manel Jordana

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Figure 1

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Airway eosinophilia in BAL of C57BL/6 (WT) and LT-α–deficient (LTα-KO) m...
Airway eosinophilia in BAL of C57BL/6 (WT) and LT-α–deficient (LTα-KO) mice exposed to aerosolized OVA in the context of GM-CSF expression. Over a period of 10 consecutive days, mice were exposed daily to OVA. Twenty-four hours before first exposure, mice were infected intranasally with adenoviral construct expressing GM-CSF. Data were obtained 48 hours after last exposure to OVA. (Mean ± SEM; n = 4–6; statistical analysis was performed using one-way ANOVA with Fisher’s post hoc test; *P < 0.05.)