Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response. CD8(+) T cells are implicated in COPD pathogenesis, and their numbers significantly correlate with the degree of airflow limitation. Dendritic cells (DCs) are important sentinel immune cells, but little is known about their role in initiating and maintaining the CD8 T-cell response in COPD. To investigate the mechanisms for CD8(+) T-cell recruitment to the lung, we used resected human lung tissue to analyze chemokine receptor expression by CD8(+) T cells and chemokine production by CD1a(+) DCs. Among 11 surveyed chemokine receptors, only CC chemokine receptor (CCR5), CXC chemokine receptor (CXCR) 3, and CXCR6 correlated with COPD severity as defined by criteria from the Global Initiative for Chronic Obstructive Lung Disease. The CD8(+) T cells displayed a Tc1, CD45RA(+) effector memory phenotype. CD1a(+) DCs produced the respective ligands for CCR5 and CXCR3, CCL3 and CXCL9, and levels correlated with disease severity. CD1a(+) DCs also constitutively expressed the CXCR6 ligand, CXCL16. In conclusion, we have identified major chemokine elements that potentially mediate CD8(+) T-cell infiltration during COPD progression and demonstrated that CD1a(+) mucosal-associated DCs may sustain CD8(+) T-cell recruitment/retention. Chemokine targeting may prove to be a viable treatment approach.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Adult
- Aged
- Animals
- Antigens, CD / genetics
- Antigens, CD / metabolism
- Antigens, CD1 / genetics
- Antigens, CD1 / metabolism
- CD8-Positive T-Lymphocytes / cytology
- CD8-Positive T-Lymphocytes / immunology*
- CD83 Antigen
- Cell Separation
- Chemokine CCL3 / genetics
- Chemokine CCL3 / metabolism
- Chemokine CXCL16
- Chemokine CXCL9 / genetics
- Chemokine CXCL9 / metabolism
- Chemokines, CXC / genetics
- Chemokines, CXC / metabolism
- Dendritic Cells / cytology
- Dendritic Cells / metabolism
- Humans
- Immunoglobulins / genetics
- Immunoglobulins / metabolism
- Lung* / cytology
- Lung* / immunology
- Lung* / pathology
- Membrane Glycoproteins / genetics
- Membrane Glycoproteins / metabolism
- Middle Aged
- Phenotype
- Pulmonary Disease, Chronic Obstructive* / immunology
- Pulmonary Disease, Chronic Obstructive* / pathology
- Pulmonary Disease, Chronic Obstructive* / physiopathology
- Receptors, CCR5 / genetics
- Receptors, CCR5 / metabolism*
- Receptors, CXCR3 / genetics
- Receptors, CXCR3 / metabolism
- Receptors, CXCR6
- Receptors, Chemokine / genetics
- Receptors, Chemokine / metabolism*
- Receptors, Scavenger / genetics
- Receptors, Scavenger / metabolism
- Receptors, Virus / genetics
- Receptors, Virus / metabolism*
Substances
- Antigens, CD
- Antigens, CD1
- CCL3 protein, human
- CD1a antigen
- CXCL16 protein, human
- CXCL9 protein, human
- CXCR3 protein, human
- CXCR6 protein, human
- Chemokine CCL3
- Chemokine CXCL16
- Chemokine CXCL9
- Chemokines, CXC
- Immunoglobulins
- Membrane Glycoproteins
- Receptors, CCR5
- Receptors, CXCR3
- Receptors, CXCR6
- Receptors, Chemokine
- Receptors, Scavenger
- Receptors, Virus