Am. J. Respir. Cell Mol. Biol., Volume 22, Number 4, April, 2000 491-501

Interferon- Production by Specific Lung Lymphocyte Phenotypes in Silicosis in Mice

Gerald S. Davis, Linda M. Pfeiffer, and David R. Hemenway

Departments of Medicine and Civil & Mechanical Engineering, University of Vermont, Burlington, Vermont

We recently described overproduction of interferon (IFN)- by lung lymphocytes in mice with silicosis (11% of cells in air-control versus 19% of cells from silica-exposed mice; Davis and colleagues, Am. J. Respir. Cell Mol. Biol. 1999;20:813-824). We hypothesized that the increased IFN- production might be due to selective enrichment of one lymphocyte phenotype. To test this hypothesis, small mononuclear cells from lung digest preparations of mice exposed 4 mo previously to cristobalite silica (70 mg/m³, 12 d, 5 h/d) or to sham-air were stained for intracellular cytokines and surface antigen phenotypes, and examined by flow cytometry. Air-sham mouse lung digests included CD4⁺ (16%) and CD8⁺ (6%) T cells, T-cell antigen receptor (TCR)⁺ CD4CD8 T cells (3%), natural killer (NK) cells (15%), B cells (6%), and macrophages (12%). The total number of lung lymphocytes was increased 1.7-fold in silicosis, but the phenotype frequencies did not change significantly. In the control lungs IFN- was produced by three major phenotypes of lymphocytes: 5% of CD4⁺ T cells, 5% of -TCR⁺ CD4CD8 T cells, and 2% of NK cells. The percentage of each type producing IFN- was increased 2- to 3-fold in silicosis. When multiplied by cell number, the increased percentages yielded a 3- to 5-fold increase in the total number of each IFN- -producing phenotype in the lung. Our results demonstrate no selective phenotype enrichment but upregulated IFN- production by at least three lymphocyte phenotypes. IFN- may be an important signal driving lymphocyte differentiation and macrophage activation in silicosis.

This article has been cited by other articles:

				T. Sato, T. Shimosato, W. G. Alvord, and D. M. Klinman Suppressive Oligodeoxynucleotides Inhibit Silica-Induced Pulmonary Inflammation J. Immunol., June 1, 2008; 180(11): 7648 - 7654. [Abstract] [Full Text] [PDF]

				A. Shukla, K. M. Lounsbury, T. F. Barrett, J. Gell, M. Rincon, K. J. Butnor, D. J. Taatjes, G. S. Davis, P. Vacek, K. I. Nakayama, et al. Asbestos-Induced Peribronchiolar Cell Proliferation and Cytokine Production Are Attenuated in Lungs of Protein Kinase C-{delta} Knockout Mice Am. J. Pathol., January 1, 2007; 170(1): 140 - 151. [Abstract] [Full Text] [PDF]

				P. Misson, F. Brombacher, M. Delos, D. Lison, and F. Huaux Type 2 immune response associated with silicosis is not instrumental in the development of the disease Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L107 - L113. [Abstract] [Full Text] [PDF]

				M. T. Borchers, N. L. Harris, S. C. Wesselkamper, M. Vitucci, and D. Cosman NKG2D ligands are expressed on stressed human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L222 - L231. [Abstract] [Full Text] [PDF]

				R. Loi, T. Beckett, K. K. Goncz, B. T. Suratt, and D. J. Weiss Limited Restoration of Cystic Fibrosis Lung Epithelium In Vivo with Adult Bone Marrow-derived Cells Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 171 - 179. [Abstract] [Full Text] [PDF]

				V. Barbarin, M. Arras, P. Misson, M. Delos, B. McGarry, S. H. Phan, D. Lison, and F. Huaux Characterization of the Effect of Interleukin-10 on Silica-Induced Lung Fibrosis in Mice Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 78 - 85. [Abstract] [Full Text] [PDF]

				E. I. Majeski, M. K. Paintlia, A. D. Lopez, R. A. Harley, S. D. London, and L. London Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes Am. J. Pathol., October 1, 2003; 163(4): 1467 - 1479. [Abstract] [Full Text] [PDF]

				E. I. Majeski, R. A. Harley, S. C. Bellum, S. D. London, and L. London Differential Role for T Cells in the Development of Fibrotic Lesions Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia versus Acute Respiratory Distress Syndrome Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 208 - 217. [Abstract] [Full Text] [PDF]

				F. Huaux, M. Arras, D. Tomasi, V. Barbarin, M. Delos, J.-P. Coutelier, A. Vink, S. H. Phan, J.-C. Renauld, and D. Lison A Profibrotic Function of IL-12p40 in Experimental Pulmonary Fibrosis J. Immunol., September 1, 2002; 169(5): 2653 - 2661. [Abstract] [Full Text] [PDF]

				V. M. Borges, M. F. Lopes, H. Falcao, J. H. Leite-Junior, P. R. M. Rocco, W. F. Davidson, R. Linden, W. A. Zin, and G. A. DosReis Apoptosis Underlies Immunopathogenic Mechanisms in Acute Silicosis Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 78 - 84. [Abstract] [Full Text] [PDF]

				A. K. Hubbard, C. R. Timblin, A. Shukla, M. Rincon, and B. T. Mossman Activation of NF-kappa B-dependent gene expression by silica in lungs of luciferase reporter mice Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L968 - L975. [Abstract] [Full Text] [PDF]