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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Simonian, Philip L. Martin, Allison K. Hoover, Mark D. Mack, Douglas G. Kappler, John W. Gordon, Terry Marrack, Philippa Tuder, Rubin M. Fontenot, Andrew P. Crawford, Frances Falta, Michael T. Mckee, Amy S. Mercer, Robert R. |
| Description | Author Affiliation: Mack DG ( Departments of Medicine and.); Falta MT ( Departments of Medicine and.); McKee AS ( Departments of Medicine and.); Martin AK ( Departments of Medicine and.); Simonian PL ( Departments of Medicine and.); Crawford F ( Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045); Gordon T ( Department of Environmental Medicine, New York University, Tuxedo, NY 10987); Mercer RR ( National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505); Hoover MD ( National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505); Marrack P ( Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045); Kappler JW ( Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045); Tuder RM ( Departments of Medicine and.); Fontenot AP ( Departments of Medicine andImmunology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045); |
| Abstract | Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP molecules, including HLA-DP2. To elucidate the molecular basis of this association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed mononuclear infiltrates in a peribronchovascular distribution that were composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium-responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-γ and IL-2 were present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA-DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung that recognize identical ligands as CD4(+) T cells derived from the human lung. Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed forkhead box P3, consistent with the expansion of antigen-specific Treg cells. Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung inflammation and enhanced granuloma formation. These findings document, for the first time to our knowledge, the development of a Be-specific adaptive immune response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the beryllium-induced granulomatous immune response. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Berylliosis Immunology Disease Models, Animal Granuloma HLA-DP Beta-Chains Inflammation T-Lymphocytes, Regulatory Adaptive Immunity Genetics Animals Beryllium Bronchoalveolar Lavage Fluid Cytology CD4-Positive T-Lymphocytes Metabolism Enzyme-Linked Immunospot Assay Flow Cytometry Forkhead Transcription Factors Interferon-gamma Interleukin-2 Lung Pathology Mice Mice, Transgenic Spleen Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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