TNF-α negatively modulates allergen-induced airway hyperresponsiveness through γδ T cells
A. Kanehiro, M. Lahn, M. J. Mäkelä, A. Dakhama, M. Fujita, M. Tanimoto, R. J. Mason, W. Born, E. W. Gelfand (Okayama, Japan; Denver, United States Of America)
Source: Annual Congress 2002 - Cellular reactions in allergy in humans and animals
Session: Cellular reactions in allergy in humans and animals
Session type: Poster Discussion
Number: 294
Disease area: Airway diseases
Abstract Tumor necrosis factor (TNF)-α is a potent cytokine with immunomodulatory, proinflammatory and pathobiological activities. Although TNF-α is thought to play a role in mediating airway hyperresponsiveness (AHR) in asthma, its function is not defined. To address this issue, TNF-α deficient mice and TNF-α transgenic mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways; airway function to inhaled methacholine was monitored. In TNF-α deficient mice, AHR was significantly increased compared to controls (p<0.05). In contrast, TNF-α transgenic mice failed to develop AHR. In addition, sensitized/challenged TNF-α deficient mice demonstrated significantly elevated numbers of eosinophils, and higher levels of IL-5 and IL-10 in bronchoalveolar lavage fluid (BALF) compared to control mice (p<0.05). However, in TNF-α transgenic mice both the numbers of eosinophils and levels of IL-5 and IL-10 were significantly lower than in sensitized/challenged wild type mice (p<0.05). γδ T cells have been shown to be activated by TNF-α and to negatively regulate AHR. Depletion of γδ T cells in the TNF-α transgenic mice increased AHR, whereas this depletion had no significant effect in TNF-α deficient mice. These data indicate that TNF-α can negatively modulate airway responsiveness, controlling airway function in allergen-induced AHR through the activation of γδ T cells.
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A. Kanehiro, M. Lahn, M. J. Mäkelä, A. Dakhama, M. Fujita, M. Tanimoto, R. J. Mason, W. Born, E. W. Gelfand (Okayama, Japan; Denver, United States Of America). TNF-α negatively modulates allergen-induced airway hyperresponsiveness through γδ T cells. Eur Respir J 2002; 20: Suppl. 38, 294
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