Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen-specific T cells and airway inflammation in a murine model of asthma.
T cells expressing a type-2 T helper profile of cytokines (Th2 cells) have been demonstrated to play an important role in the initiation and progression of allergic asthma, and it is well known that Fas ligand (FasL) induces apoptosis when bound to its receptor, Fas. In the present study, we examined the possibility of modulating asthma manifestations by dendritic cells (DCs) genetically engineered to express FasL (DC-FasL), which could deliver a death signal to T cells in an antigen-specific manner. The delivery of DC-FasL into ovalbumin (OVA)-immunized allergic mice decreased the airway hyper-responsiveness (AHR). Moreover, we established a mouse model of airway inflammation by using an adoptive transfer of Th2 cells derived from ovalbumin T cell receptor transgenic mice to study the effect of DC-FasL on airway reactivity. The administration of DC-FasL in Th2-cell-induced allergic mice had significantly decreased AHR, airway inflammation, and IL-4, IL-5 and IL-13 production. Furthermore, the numbers of OVA-specific T cells were decreased in the lung of mice receiving DC-FasL. These results demonstrate that FasL-expressing dendritic cells might be applied for the modulation of allergic responses.
Graduate Institute of Immunology, National Taiwan University, Taiwan, Republic of China.
Ya-Hui
YH
Chuang
Jau-Ling
JL
Suen
Bor-Luen
BL
Chiang
D000256:Adenoviridae / Q000235:genetics; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection
D000485:Allergens; D016207:Cytokines; D053222:Fas Ligand Protein; D010047:Ovalbumin