Abstract
T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma-dominant) or type 2 (IL-4-, IL-5-dominant) patterns. To investigate mechanisms that connect extracellular stimuli with the regulation of effector T cell function, we have measured immune responses of transgenic mice whose NF-kappa B/Rel signaling pathway is inhibited in T cells. Surprisingly, these mice developed type 2 T cell-dependent responses (IgE and eosinophil recruitment) in a model of allergic pulmonary inflammation. In contrast, type 1 T cell responses were severely impaired, as evidenced by markedly diminished delayed-type hypersensitivity responses, IFN-gamma production, and Ag-specific IgG2a levels. Taken together, these data indicate that inhibition of NF-kappa B can lead to preferential impairment of type 1 as compared with type 2 T cell-dependent responses.
Publication types
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Comparative Study
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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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Animals
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Bronchial Hyperreactivity / genetics
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Bronchial Hyperreactivity / immunology
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Bronchial Hyperreactivity / pathology
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Cell Movement / genetics
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Cell Movement / immunology
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Cytokines / biosynthesis
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DNA-Binding Proteins / genetics
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Eosinophilia / genetics
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Eosinophilia / immunology
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Eosinophilia / pathology
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Hypersensitivity, Delayed / genetics
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Hypersensitivity, Delayed / immunology
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I-kappa B Proteins*
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Immunoglobulin Isotypes / biosynthesis
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Lung / immunology
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Lung / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Transgenic
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / physiology*
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Proto-Oncogene Proteins c-rel / antagonists & inhibitors
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Proto-Oncogene Proteins c-rel / physiology*
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Respiratory Hypersensitivity / genetics
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Respiratory Hypersensitivity / immunology
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Respiratory Hypersensitivity / pathology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Transcription Factor RelA
Substances
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Cytokines
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DNA-Binding Proteins
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I-kappa B Proteins
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Immunoglobulin Isotypes
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NF-kappa B
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Nfkbia protein, mouse
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Proto-Oncogene Proteins c-rel
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Transcription Factor RelA
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NF-KappaB Inhibitor alpha