Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease.

TitleLung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsFreeman CM, Martinez FJ, Han MLK, Ames TM, Chensue SW, Todt JC, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL
JournalAm J Respir Crit Care Med
Volume180
Issue12
Pagination1179-88
Date Published2009 Dec 15
ISSN1535-4970
KeywordsAged, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Cell Culture Techniques, Cell Differentiation, Cross-Sectional Studies, Dendritic Cells, Female, Flow Cytometry, Humans, Lectins, C-Type, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Smoking
Abstract

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).

DOI10.1164/rccm.200904-0552OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID19729666
PubMed Central IDPMC2796731
Grant ListK24 HL004212 / HL / NHLBI NIH HHS / United States
K24HL04212 / HL / NHLBI NIH HHS / United States
KL2 RR024987 / RR / NCRR NIH HHS / United States
N01 HR046162 / HR / NHLBI NIH HHS / United States
P30 CA46952 / CA / NCI NIH HHS / United States
R01 CA094121 / CA / NCI NIH HHS / United States
R01 CA094121-05 / CA / NCI NIH HHS / United States
R01 HL082480 / HL / NHLBI NIH HHS / United States
T32 HL07749 / HL / NHLBI NIH HHS / United States