Abstract
Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-gamma, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-gamma and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-gamma production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-gamma by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-gamma-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.
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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Alveolitis, Extrinsic Allergic / immunology*
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Alveolitis, Extrinsic Allergic / pathology
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Antigens, CD / biosynthesis
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Antigens, CD / blood
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B7-1 Antigen / biosynthesis
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B7-1 Antigen / blood
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B7-2 Antigen
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Cytokines / biosynthesis*
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Cytokines / blood
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Cytokines / genetics
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Gene Expression / immunology
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / blood
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Interleukin-10 / biosynthesis
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Interleukin-10 / blood
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Interleukin-10 / physiology
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Interleukin-12 / biosynthesis
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Interleukin-12 / blood
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Interleukin-12 / metabolism
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Interleukin-12 / physiology
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Interleukin-2 / biosynthesis
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Interleukin-2 / blood
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Leukocytes, Mononuclear / metabolism
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Macrophages, Alveolar / metabolism
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Macrophages, Alveolar / physiology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / blood
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Monocytes / metabolism
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Monocytes / physiology
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Muromonab-CD3 / pharmacology
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-12
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Reverse Transcriptase Polymerase Chain Reaction
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Th1 Cells / metabolism*
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Th1 Cells / pathology
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CD86 protein, human
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Cytokines
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Interleukin-2
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Membrane Glycoproteins
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Muromonab-CD3
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Receptors, Interleukin
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Receptors, Interleukin-12
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Interleukin-10
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Interleukin-12
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Interferon-gamma