title: Polarized type 1 cytokine profile in bronchoalveolar lavage T cells of patients with hypersensitivity pneumonitis.
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.
authors.affiliation: First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: W
authors.initials: W
authors.lastname: Brazer
authors.forename: D M
authors.initials: DM
authors.lastname: Center
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000097:blood; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D016853:Muromonab-CD3 / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000378:metabolism; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma