CD8+ T cells contribute to macrophage accumulation and airspace enlargement following repeated irritant exposure.
BACKGROUND
Persistent macrophage accumulation and alveolar enlargement are hallmark features of chronic obstructive pulmonary disease (COPD). A role for CD8(+) lymphocytes in the development of COPD is suggested based on observations that this T cell subset is increased in the airways and parenchyma of smokers that develop COPD with airflow limitation. In this study, we utilize a mouse model of COPD to examine the contributions of CD8(+) T cells in the persistent macrophage accumulation and airspace enlargement resulting from chronic irritant exposure.


METHODS
We analyzed pulmonary inflammation and alveolar destruction in wild-type and Cd8-deficient mice chronically exposed to acrolein, a potent respiratory tract irritant. We further examined cytokine mRNA expression levels by RNase protection assay, matrix metalloproteinase (MMP) activity by gelatin zymography, and epithelial cell apoptosis by active caspase3 immunohistochemistry in wild-type and Cd8-deficient mice exposed chronically to acrolein.


RESULTS
These studies demonstrate that CD8(+) T cells are important mediators of macrophage accumulation in the lung and the progressive airspace enlargement in response to chronic acrolein exposures. The expression of several inflammatory cytokines (IP-10, IFN-gamma, IL-12, RANTES, and MCP-1), MMP2 and MMP9 gelatinase activity, and caspase3 immunoreactivity in pulmonary epithelial cells were attenuated in the Cd8-deficient mice compared to wild-type.


CONCLUSIONS
These results indicate that CD8(+) T cells actively contribute to macrophage accumulation and the development of irritant-induced airspace enlargement.
Borchers
Michael T
MT
Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA. michael.borchers@uc.edu
Wesselkamper
Scott C
SC
Harris
Nathaniel L
NL
Deshmukh
Hitesh
H
Beckman
Erin
E
Vitucci
Mark
M
Tichelaar
Jay W
JW
Leikauf
George D
GD
D000171:Acrolein / Q000276:immunology / Q000633:toxicity; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D007509:Irritants / Q000276:immunology / Q000633:toxicity; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D012907:Smoking; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016827:CD8 Antigens; D016207:Cytokines; D007509:Irritants; D000171:Acrolein