The Journal of allergy and clinical immunology · 2002
CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation.
СтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Oh Jae-Won, Seroogy Christine M, Meyer Everett H, Akbari Omid, Berry Gerald, Fathman C Garrison, Dekruyff Rosemarie H, Umetsu Dale T
Аннотация
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.
CONCLUSION: 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.
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.
CONCLUSION: 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.
Предметные рубрики MeSH
AllergensAnimalsAsthmaBronchial HyperreactivityCell LineCytokinesDose-Response Relationship, DrugGenetic TherapyInflammationInterleukin-10Methacholine ChlorideMiceMice, Inbred BALB CMice, SCIDOvalbuminProtein EngineeringPulmonary EosinophiliaT-Lymphocytes, Helper-InducerTh2 CellsTransduction, Genetic