Abstract
Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Allergens / immunology
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Animals
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Asthma* / immunology
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Asthma* / metabolism
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Asthma* / pathology
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Bronchial Hyperreactivity / immunology
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Bronchial Hyperreactivity / metabolism
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Bronchial Hyperreactivity / pathology
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Bronchoalveolar Lavage Fluid / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / transplantation
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Collagen Type III / metabolism
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Cytokines / metabolism
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Disease Models, Animal
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Gene Targeting
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Humans
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Interleukin-4 / metabolism
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Interleukin-5 / metabolism
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Mice
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Mice, Knockout
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Mice, SCID
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T-Box Domain Proteins
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T-bet Transcription Factor
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Transcription Factors / deficiency
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription Factors / physiology*
Substances
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Allergens
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Collagen Type III
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Cytokines
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Interleukin-5
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T-Box Domain Proteins
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T-bet Transcription Factor
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Transcription Factors
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Interleukin-4