Interferon-gamma production by specific lung lymphocyte phenotypes in silicosis in mice.
We recently described overproduction of interferon (IFN)-gamma 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-gamma 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/m(3), 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, gammadelta T-cell antigen receptor (TCR)(+) CD4(-)CD8(-) 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-gamma was produced by three major phenotypes of lymphocytes: 5% of CD4(+) T cells, 5% of gammadelta-TCR(+) CD4(-)CD8(-) T cells, and 2% of NK cells. The percentage of each type producing IFN-gamma 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- gamma-producing phenotype in the lung. Our results demonstrate no selective phenotype enrichment but upregulated IFN-gamma production by at least three lymphocyte phenotypes. IFN-gamma may be an important signal driving lymphocyte differentiation and macrophage activation in silicosis.
Davis
G S
GS
Departments of Medicine and Civil & Mechanical Engineering, University of Vermont, Burlington, VT, USA. gdavis1@zoo.uvm.edu
Pfeiffer
L M
LM
Hemenway
D R
DR
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D020126:Brefeldin A / Q000494:pharmacology; D002454:Cell Differentiation; D016207:Cytokines / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype; D012822:Silicon Dioxide; D012829:Silicosis / Q000276:immunology* / Q000473:pathology
D000954:Antigens, Surface; D016207:Cytokines; D020126:Brefeldin A; D012822:Silicon Dioxide; D007371:Interferon-gamma