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CCR5 and CXCR6 expression on lung CD8+ T cells correlates with COPD severity
Author(s) -
Freeman Christine,
Curtis Jeffrey L.,
Chensue Stephen W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a209-c
Subject(s) - copd , chemokine , cd8 , immunology , medicine , lung , chemokine receptor , flow cytometry , pathogenesis , ccr4 , inflammation , antigen
RATIONALE Chronic obstructive pulmonary disease (COPD) is characterized by progressive, irreversible airflow limitation associated with increased numbers of CD8+ T cells, neutrophils, and macrophages. Lung CD8+ T cells appear central to COPD pathogenesis as their numbers correlate with stage of disease, but the factors regulating their accumulation are unknown. METHODS: To identify novel therapeutic targets, we analyzed chemokine systems that might attract CD8+ T cells to the airways. We used fresh human lung resected for clinical indications from smokers with or without COPD. Samples were classified as having mild, moderate, and severe COPD, based on GOLD criteria. We isolated lung CD8+ T cells and CD1a+ dendritic cells (DC) and analyzed mRNA for chemokines and chemokine receptors by real time RT‐PCR. Surface expression of chemokine receptors was confirmed by flow cytometry. RESULTS: Among lung CD8 + T cells, transcript levels increased with worsening COPD severity and correlated significantly with stage for CCR5 (R = 0.75) and CXCR6 (R = 0.72). Lung DC mRNA levels of CCL3, a CCR5 ligand, also increased with COPD severity (R = 0.72). CONCLUSIONS: CCR5 and CXCR6 are potential targets for novel therapies to block CD8+ T cell infiltration of the lungs in COPD. In addition, CD1a+ DC may contribute to CD8+ T cell recruitment. Supported by the VA Research Enhancement Award Program.