title: Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma.
abstract: Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)gamma production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNgamma-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Tong
authors.forename: Hozefa S
authors.initials: HS
authors.lastname: Bandulwala
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Clay
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Shilling
authors.forename: Diwakar D
authors.initials: DD
authors.lastname: Balachandran
authors.forename: Bohao
authors.initials: B
authors.lastname: Chen
authors.forename: Joel V
authors.initials: JV
authors.lastname: Weinstock
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
authors.forename: Kimm J
authors.initials: KJ
authors.lastname: Hamann
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002908:Chronic Disease; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D013997:Time Factors; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
chemical_list: D019014:fas Receptor; D007371:Interferon-gamma