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(Chest. 2004;125:107S.)
© 2004 American College of Chest Physicians

Selective Suppression of Dendritic Cell Functions by Cigarette Smoke Extract*

Robert Vassallo, MD, FCCP and Lieping Chen, MD, PhD

* From the Mayo Clinic, Rochester, MN.

Correspondence to: Robert Vassallo, MD, FCCP, Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Stabile Bldg 8–54, Rochester, MN 55905; e-mail: vassallo.robert{at}mayo.edu

Dendritic cells are potent antigen-presenting cells and critical regulators of T-cell responses. We postulated that an important mechanism by which smoking predisposes a person to cancer is by suppressing dendritic cell function, thus inhibiting the ability of dendritic cells to stimulate appropriate T-cell responses. To test this hypothesis, human monocyte-derived dendritic cells were incubated with freshly prepared cigarette smoke extract (CSE) [0 to 2%; mean (± SD) nicotine content in 1% CSE, 2.3 ± 0.8 µg/mL] for the final 18 to 24 h of culture. Dendritic cells were then washed to remove all residual CSE and were incubated with allogenic purified T cells in a mixed lymphocyte reaction for 72 h. T-cell proliferation was measured by the incorporation of tritiated thymidine and cytokine levels into the mixed lymphocyte reaction measured by enzyme-linked immunosorbent assay. The transient incubation of immature dendritic cells with CSE at doses that did not affect viability (as measured by the XTT assay, trypan blue exclusion, and annexin V/propidium iodide staining) resulted in significant suppression of dendritic cell-induced T-cell proliferation. This decrease in T-cell proliferation was accompanied by reduced interferon-{gamma} production, but not in interleukin-4 or interleukin-10 secretion. Dendritic cell surface expression of major histocompatibility complex class II, major histocompatibility complex class I, CD-40, CD-80, CD-86, CD-83, and CD-1a was not altered by transient exposure (ie, for 24 h) to CSE at the same concentrations that diminished dendritic cell-induced T-cell proliferation. These data indicate that transient exposure to CSE causes the selective suppression of dendritic cell functions in the induction of T-cell proliferation and the production of interferon-{gamma}.


    Footnotes
 
Abbreviation: CSE = cigarette smoke extract

This research was supported by an American Lung Association research grant, a Parker B. Francis fellowship (RV), and National Institutes of Health grants CA79915 and CA85721 (LC).





This Article
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Right arrow Articles by Vassallo, R.
Right arrow Articles by Chen, L.


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