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Journal of Clinical Investigation (1)
The Journal of Experimental Medicine (1)
Coyle, Anthony J. (2)
Alvarez, David (1)
Gajewska, Beata U. (1)
Goncharova, Susanna (1)
Gutierrez-Ramos, Jose Carlos (1)
Gutierrez-Ramos, José-Carlos (1)
Hussell, Tracy (1)
Jordana, Manel (1)
Kendall, Sharon (1)
Matthews, Stephen (1)
Openshaw, Peter J.M. (1)
Stämpfli, Martin R. (1)
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Walzl, Gerhard (1)
Year of Publication
Inhibition of T1/St2 during Respiratory Syncytial Virus Infection Prevents T Helper Cell Type 2 (Th2)- but Not Th1-Driven Immunopathology
Gutierrez-Ramos, Jose Carlos
Openshaw, Peter J.M.
The Journal of Experimental Medicine
T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-γ–producing Th1 cells. Prior exposure of BALB/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1/ST2 cells to the lung and to test the effects of anti-T1/ST2 treatment in vivo. T1/ST2 was present on a subset of CD4+ cells from mice with eosinophilic lung disease. Monoclonal anti-T1/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.
bronchiolitis, viral; immunity, mucosal; immunity, cellular; pulmonary infection; eosinophil
Generation of experimental allergic airways inflammation in the absence of draining lymph nodes
Gajewska, Beata U.
Stämpfli, Martin R.
Journal of Clinical Investigation
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.
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