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Cigarette Smoke Exposure Impairs Dendritic Cell Maturation and T Cell Proliferation in Thoracic Lymph Nodes of Mice¹

Clinton S. Robbins^2,*, Francesca Franco^2,,, Majd Mouded^*, Manuela Cernadas and Steven D. Shapiro^3,*

^* Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261; Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and Section of Respiratory Disease, Department of Oncology, Haematology, and Respiratory Disease, University of Modena and Reggio Emilia, Modena, Italy

Respiratory tract dendritic cells (DCs) are juxtaposed to directly sample inhaled environmental particles. Processing and presentation of these airborne Ags could result in either the development of immunity or tolerance. The purpose of this study was to determine the consequences of cigarette smoke exposure on DC function in mice. We demonstrate that while cigarette smoke exposure decreased the number of DCs in the lungs, Ag-induced DC migration to the regional thoracic lymph nodes was unaffected. However, cigarette smoking suppressed DC maturation within the lymph nodes as demonstrated by reduced cell surface expression of MHC class II and the costimulatory molecules CD80 and CD86. Consequently, DCs from cigarette smoke-exposed animals had a diminished capacity to induce IL-2 production by T cells that was associated with diminished Ag-specific T cell proliferation in vivo. Smoke-induced defects in DC function leading to impaired CD4⁺ T cell function could inhibit tumor surveillance and predispose patients with chronic obstructive pulmonary disease to infections and exacerbations.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HL029594 and HL054853.

² C.S.R. and F.F. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Steven D. Shapiro, Department of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261. E-mail address: Shapiros{at}dom.pitt.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; TLN, thoracic lymph node; i.t., intratracheal; AF, autofluorescence; MHCII, MHC class II; Treg, T regulatory cell.