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Published ahead of print on August 14, 2003, doi:10.1165/rcmb.2003-0259OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 202-211, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0259OC

Cigarette Smoke Decreases Pulmonary Dendritic Cells and Impacts Antiviral Immune Responsiveness

Clinton S. Robbins, David E. Dawe, Susanna I. Goncharova, Mahmoud A. Pouladi, Anna G. Drannik, Filip K. Swirski, Gerard Cox and Martin R. Stämpfli

Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Address correspondence to: Martin R. Stämpfli, Ph.D., McMaster University, Department of Pathology and Molecular Medicine, Health Sciences Centre, Room 4H21A, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: stampfli{at}mcmaster.ca

We investigated the impact of cigarette smoke exposure on respiratory immune defense mechanisms. Mice were exposed to two cigarettes daily, 5 d/wk, for 2–4 mo. Tobacco smoke decreased the number of dendritic cells (DCs) in the lung tissue. Furthermore, smoke exposure dramatically reduced the percentage of B7.1-expressing DCs. Because DCs are believed to be indispensable to the initiation of adaptive immune responses, we investigated the impact of cigarette smoke on immune responsiveness toward adenovirus. Mice were exposed to two cigarettes for 2–4 mo and inoculated with 2 x 108 pfu of a replication-deficient adenovirus on three occasions, 2 wk apart, during the last month of tobacco smoke exposure. Smoke exposure specifically prevented the expansion and maximal activation of CD4 T cells and reduced the number of both activated CD4 and CD8 T cells. Consequently, smoke exposure shifted the activated CD4:CD8 T cell ratio from 3 to 1.5 when compared with sham exposure. Significant decreases were also observed in serum adenovirus-specific pan IgG, IgG1, and IgG2a immunoglobulin levels, which was associated with diminished viral neutralization capacity. We demonstrate that chronic tobacco smoke exposure impairs the immune response against adenovirus. This may, in part, explain the increased prevalence of viral infections in chronic obstructive pulmonary disease.

Abbreviations: adenovirus, Ad • antigen-presenting cells, APCs • chronic obstructive pulmonary disease, COPD • cytotoxic lymphocytes, CTL • dendritic cells, DCs • enzyme-linked immunosorbent assay, ELISA • fluorescein isothiocyanate, FITC • Hanks' balanced salt solution, HBSS • interferon-{gamma}, IFN-{gamma} • interleukin, IL • phycoerythrin, PE




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