T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production.
CD4 T helper (Th) type 1 and Th2 cells have been identified in the airways of asthmatic patients. Th2 cells are believed to contribute to pathogenesis of the disease, but the role of Th1 cells is not well defined. In a mouse model, we previously reported that transferred T cell receptor-transgenic Th2 cells activated in the respiratory tract led to airway inflammation with many of the pathologic features of asthma, including airway eosinophilia and mucus production. Th1 cells caused inflammation with none of the pathology associated with asthma. In this report, we investigate the role of Th1 cells in regulating airway inflammation. When Th1 and Th2 cells are transferred together into recipient mice, there is a marked reduction in airway eosinophilia and mucus staining. To address the precise role of Th1 cells, we asked (i), Are Th2-induced responses inhibited by interferon (IFN)-gamma? and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma? In IFN-gamma receptor(-/-) recipient mice exposed to inhaled antigen, the inhibitory effects of Th1 cells on both airway eosinophilia and mucus production were abolished. In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia. Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma. The blockade of eosinophilia and mucus production by IFN-gamma likely occurs through different inhibitory pathways that are activated downstream of Th2 cytokine secretion and require IFN-gamma signaling in tissue of recipient mice.
Cohn
L
L
Section of Pulmonary Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lauren.cohn@yale.edu
Homer
R J
RJ
Niu
N
N
Bottomly
K
K
D000818:Animals; D001249:Asthma / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D007378:Interleukins; D017471:Receptors, Interferon; D007371:Interferon-gamma; D010047:Ovalbumin