CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation.
BACKGROUND
T(H)2 cells play a critical role in the pathogenesis of asthma, but the precise immunologic mechanisms that inhibit T(H)2 cell function in vivo are not well understood.


OBJECTIVE
The purpose of our studies was to determine whether T cells producing IL-10 regulate the development of asthma.


METHODS
We used gene therapy to generate ovalbumin-specific CD4 T-helper cells to express IL-10, and we examined their capacity to regulate allergen-induced airway hyperreactivity.


RESULTS
We demonstrated that the CD4 T-helper cells engineered to express IL-10 abolished airway hyperreactivity and airway eosinophilia in BALB/c mice sensitized and challenged with ovalbumin and in SCID mice reconstituted with ovalbumin-specific T(H)2 effector cells. The inhibitory effect of the IL-10-secreting T-helper cells was accompanied by the presence of increased quantities of IL-10 in the bronchoalveolar lavage fluid, was antigen-specific, and was reversed by neutralization of IL-10. Moreover, neutralization of IL-10 by administration of anti-IL-10 mAb in mice sensitized and challenged with ovalbumin seriously exacerbated airway hyperreactivity and airway inflammation.


CONCLUSIONS
Our results demonstrate that T cells secreting IL-10 in the respiratory mucosa can indeed regulate T(H)2-induced airway hyperreactivity and inflammation, and they strongly suggest that IL-10 plays an important inhibitory role in allergic asthma.
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, CA 94305, USA.
Jae-Won
JW
Oh
Christine M
CM
Seroogy
Everett H
EH
Meyer
Omid
O
Akbari
Gerald
G
Berry
C Garrison
CG
Fathman
Rosemarie H
RH
Dekruyff
Dale T
DT
Umetsu
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010047:Ovalbumin / Q000276:immunology; D015202:Protein Engineering; D011657:Pulmonary Eosinophilia / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology; D014161:Transduction, Genetic
D000485:Allergens; D016207:Cytokines; D016210:Methacholine Chloride; D016753:Interleukin-10; D010047:Ovalbumin