Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile.
To investigate the modulatory role of IFN-gamma on the induction and maintenance of Th2 mucosal immunity in vivo, experiments were performed in mice lacking the IFN-gamma R. Aerosol OVA challenge of immunized wild-type mice resulted in an infiltration of eosinophils into the lung, associated with the ex vivo production of Th2 cytokines (IL-4 and IL-5) from purified lung Thy1.2+ cells stimulated via the CD3/TCR complex. However, while immunized IFN-gamma R-deficient mice exhibited elevated levels of IgE, IgG1, and reduced levels of IgG2a compared with wild-type mice, there was no difference in the recruitment of eosinophils into the lung or the production of IL-4 and IL-5 from lung T cells on day 3. In contrast, up to 2 mo after a single Ag challenge, eosinophils were still present in the lungs of IFN-gamma R-deficient, but not wild-type, mice. Likewise, lung-derived T cells from IFN-gamma R-deficient mice produced higher levels of IL-4 and IL-5, both at 1 and 2 mo after OVA challenge compared with T cells from wild-type mice. We conclude that endogenous IFN-gamma regulates the humoral isotype Ab pattern, but does not modulate the commitment of T cells to a Th2 phenotype in vivo or the acute infiltration of eosinophils to the lung. However, in the absence of IFN-gamma-mediated signaling, there is a transition from a spontaneously resolving to a persisting eosinophilic inflammation of the lungs, associated with a sustained capacity of lung T cells to secrete a Th2 cytokine profile.
Coyle
A J
AJ
Department of Allergy and Asthma Research, CIBA-GEIGY Ltd., Basel, Switzerland.
Tsuyuki
S
S
Bertrand
C
C
Huang
S
S
Aguet
M
M
Alkan
S S
SS
Anderson
G P
GP
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D007371:Interferon-gamma / Q000172:deficiency; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics*; D018418:Th2 Cells / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D016207:Cytokines; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor