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Lung Dendritic Cell Expression of Maturation Molecules Increases with Worsening Chronic Obstructive Pulmonary Disease

¹ Pulmonary and Critical Care Medicine Section, VA Ann Arbor Healthcare System, Ann Arbor; ² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor; ³ Pathology & Laboratory Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor; and ⁴ Department of Pathology and ⁵ Graduate Program in Immunology, University of Michigan Health System, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Jeffrey L. Curtis, M.D., Pulmonary and Critical Care Medicine Section (506/111G), Department of Veterans Affairs Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105-2303. E-mail: jlcurtis{at}umich.edu

Rationale: Dendritic cells (DCs) have not been well studied in chronic obstructive pulmonary disease (COPD), yet their integral role in activating and differentiating T cells makes them potential participants in COPD pathogenesis.

Objectives: To determine the expression of maturation molecules by individual DC subsets in relationship to COPD stage and to expression of the acute activation marker CD69 by lung CD4⁺ T cells.

Methods: We nonenzymatically released lung leukocytes from human surgical specimens (n = 42) and used flow cytometry to identify three DC subsets (mDC1, mDC2, and pDC) and to measure their expression of three costimulatory molecules (CD40, CD80 and CD86) and of CD83, the definitive marker of DC maturation. Spearman nonparametric correlation analysis was used to identify significant correlations between expression of DC maturation molecules and COPD severity.

Measurements and Main Results: Expression of CD40 by mDC1 and mDC2 and of CD86 by mDC2 was high regardless of GOLD stage, but CD80 and CD83 on these two DC subsets increased with disease progression. pDC also showed significant increases in expression of CD40 and CD80. Expression of all but one of the DC molecules that increased with COPD severity also correlated with CD69 expression on lung CD4⁺ T cells from the same patients, with the exception of CD83 on mDC2.

Conclusions: This cross-sectional study implies that COPD progression is associated with significant increases in costimulatory molecule expression by multiple lung DC subsets. Interactions with lung DCs may contribute to the immunophenotype of CD4⁺ T cells in advanced COPD.

Clinical trial registered with www.clinicaltrials.gov (NCT00281229).

Key Words: human • flow cytometry • B70 costimulatory molecules • CD69 antigen • CD4⁺ • T lymphocytes

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Dendritic cells (DCs) are necessary to activate and induce differentiation of naive and effector T cells in response to antigens. However, the few studies that have addressed the involvement of lung DCs in chronic obstructive pulmonary disease (COPD) have found conflicting answers and have not examined maturational state as a function of disease stage. What This Study Adds to the Field DC subsets from human lungs showed increased costimulatory molecule expression that correlated with COPD severity and was not explained by smoking alone. Lung DCs colocalized with CD4+ T cells, and expression of DC activation markers correlated with expression of CD69, an early and transient marker of T-cell activation, on CD4+ T cells from the same patients.

 

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