Tumor necrosis factor-alpha negatively regulates airway hyperresponsiveness through gamma-delta T cells.

Abstract

Tumor necrosis factor (TNF)-alpha is a potent cytokine with immunomodulatory, proinflammatory, and pathobiologic activities. Although TNF-alpha is thought to play a role in mediating airway inflammation and airway hyperresponsiveness (AHR), its function is not well defined. TNF-alpha-deficient mice and mice expressing TNF-alpha in their lungs because of a TNF-alpha transgene placed under the control of the surfactant protein (SP)-C promoter (SP-C/TNF-alpha-transgenic mice) were sensitized to ovalbumin (OVA) and subsequently challenged with OVA via the airways; airway function in response to inhaled methacholine was monitored. In the TNF-alpha-deficient mice, AHR was significantly increased over that in controls. In contrast, the transgenic mice failed to develop AHR. In addition, sensitized/ challenged TNF-alpha-deficient mice had significantly increased numbers of eosinophils and higher levels of interleukin (IL)-5 and IL-10 in their bronchoalveolar lavage fluid than were found for control mice. However, in SP-C/TNF-alpha-transgenic mice, both the numbers of eosinophils and levels of IL-5 and IL-10 were significantly lower than in sensitized/challenged transgene-negative mice. gammadelta T cells have been shown to be activated by TNF-alpha and to negatively regulate AHR. Depletion of gammadelta T cells in the TNF-alpha-transgenic mice in the present study increased AHR, whereas depletion of these cells had no significant effect in TNF-alpha-deficient mice. These data indicate that TNF-alpha can negatively modulate airway responsiveness, controlling airway function in allergen-induced AHR through the activation of gammadelta T cells.

• Authors: A Kanehiro, M Lahn, M J Mäkelä, A Dakhama, M Fujita, A Joetham, R J Mason, W Born, E W Gelfand
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 164 Issue 12 Pg. 2229-38 (Dec 15 2001) ISSN: 1073-449X [Print] United States
• PMID: 11751192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Allergens
• Cytokines
• Proteolipids
• Pulmonary Surfactants
• Receptors, Antigen, T-Cell, gamma-delta
• Tumor Necrosis Factor-alpha
• Methacholine Chloride
• Immunoglobulin E
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Bronchial Hyperreactivity (metabolism, physiopathology)
• Bronchial Provocation Tests
• Cytokines (metabolism)
• Immunoglobulin E (analysis)
• Lung (metabolism, pathology)
• Lymphocyte Activation
• Methacholine Chloride
• Mice
• Mice, Transgenic
• Ovalbumin (immunology)
• Proteolipids (genetics)
• Pulmonary Surfactants (genetics)
• Receptors, Antigen, T-Cell, gamma-delta (analysis)
• T-Lymphocytes (immunology, physiology)
• Tumor Necrosis Factor-alpha (genetics, physiology)