Published online October 31, 2008
PEDIATRICS Vol. 122 Supplement November 2008, pp. S182-S183 (doi:10.1542/peds.2008-2139S)

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ALLERGY

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

Hemant P. Sharma, MD and Elizabeth C. Matsui, MD

Baltimore, MD

ABSTRACT

Robbins CS, Franco F, Mouded M, Cernadas M, Shapiro SD. J Immunol. 2008;180(10):6623–6628

PURPOSE OF THE STUDY. Airborne antigens are processed and presented by respiratory tract dendritic cells (DCs). The purpose of this study was to determine the consequences of cigarette-smoke exposure on DC function in mice.

METHODS. Mice were exposed to cigarette smoke 5 days per week for 1 month. There was also a control group of mice unexposed to smoke. Mice then underwent intratracheal injection of ovalbumin-fluorescein isothiocyanate (FITC) or ovalbumin and were killed at varying time points thereafter depending on the aspect of DC function being studied (migration, maturation, or T-cell activation). Lung cells were isolated, and the numbers of DCs were determined in exposed and unexposed mice by flow cytometry. Migration of lung DCs to thoracic lymph nodes (TLNs) was assessed by measuring CD11c⁺FITC⁺ cells. Maturation of TLN DCs after ovalbumin exposure was then determining by assessing expression of cell-surface costimulatory molecules (CD80, CD86, MHCII, CD40). T-cell proliferation was assessed by measuring T-cell–derived cytokine production by TLN cells in vitro. The staining profile was assessed to measure T-cell proliferation in vivo.

RESULTS. The number of lung DCs was decreased among mice exposed to cigarette smoke. Exposed mice did not exhibit decreased migration of lung DCs to TLNs, as evidenced by similar numbers of TLN CD11c⁺FITC⁺ cells as in unexposed mice. Although no differences were observed in migration, smoking suppressed DC maturation in the lymph nodes as demonstrated by decreased cell-surface expression of MHC class II and the costimulatory molecules CD80 and CD86. T-cell proliferation was impaired in smoke-exposed mice, evidenced by reduced interleukin 2 production from CD4 T cells as compared with controls. T-cell proliferation was also decreased in vivo: smoke-exposed mice had a lower percentage of T cells undergoing 6 cycles or cell division compared with controls.

CONCLUSIONS. These findings suggest that cigarette smoke is associated with defects in DC maturation and suppressed thoracic lymph node CD4⁺ T-cell proliferation in mice.

REVIEWER COMMENTS. This study suggests that cigarette-smoke exposure in mice leads to impaired DC maturation and thereby diminished T-cell clonal expansion in the TLNs. The findings imply that, although the T-cell effector program remains intact, fewer cells might be available to perform those duties. The authors asserted that the observed effects on DC function might serve as a potential mechanism for cigarette smoke causing impaired tumor surveillance. In addition, it is suggested that impaired CD4⁺ T-cell function might predispose patients with obstructive lung disease to infections and exacerbations. Additional studies will help to elucidate the specific mechanisms by which cigarette-smoke exposure exerts its harmful immunologic effects.

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