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Respiratory Research
Published in: Respiratory Research 1/2015

Open Access 01-12-2015 | Research

Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

Authors: Christine M. Freeman, Carlos H. Martinez, Jill C. Todt, Fernando J. Martinez, MeiLan K. Han, Deborah L. Thompson, Lisa McCloskey, Jeffrey L. Curtis

Published in: Respiratory Research | Issue 1/2015

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Abstract

Background

Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain.

Methods

We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants.

Results

Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased.

Conclusions

The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute.

Trial registration

NCT00281216, ClinicalTrials.gov.
Appendix
Available only for authorised users
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Metadata
Title
Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood
Authors
Christine M. Freeman
Carlos H. Martinez
Jill C. Todt
Fernando J. Martinez
MeiLan K. Han
Deborah L. Thompson
Lisa McCloskey
Jeffrey L. Curtis
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2015
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-015-0251-1

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