CD4+ T-Cell Profiles and Peripheral Blood Ex-Vivo Responses to T-Cell Directed Stimulation Delineate COPD Phenotypes.

ABSTRACT: The heterogeneous clinical phenotypes of chronic obstructive pulmonary disease (COPD) challenge successful drug development. To identify COPD subgroups beyond clinical phenotypes, we interrogated blood immune cell profiles and ex-vivo responses of current and former smokers, with or without COPD, in the longitudinal COPD Genetic Epidemiology study (COPDGene) cohort. CD4+ and CD8+ T cells and monocytes were profiled by flow cytometry. Microarray analysis was performed on the RNA from the aforementioned isolated cells. T-cell directed whole blood ex-vivo stimulation was used to assess functional responses. Blood CD4+ T-cell transcript analysis distinguished patients with COPD from control smokers and also enriched for a subset of patients with COPD that had a history of exacerbations of the disease. Analogous analyses of CD8+ T cells and monocytes failed to discriminate patients with COPD from the control population. Patients with COPD had a diminished cytokine response, compared to control smokers, characterized by low levels of granulocyte-monocyte colony stimulation factor (GM-CSF), interferon gamma (IFN-?), interleukin one-alpha (IL-1?), tumor necrosis factor-alpha (TNF-?) and tumor necrosis factor-beta (TNF-?) secreted in response to T-cell directed ex-vivo stimulation. This cytokine response associated with baseline disease severity (forced expiratory volume in 1 second [FEV1]% predicted), rapidly declining lung function, and emphysema. Our observations indicate that COPD phenotypes can be further differentiated based on blood CD4+ T-cell profiles and resultant immune responses, suggesting a role for these cells in COPD pathophysiology.

SUBMITTER: Roberts MEP 

PROVIDER: S-EPMC5556823 | biostudies-other | 2015 Aug

REPOSITORIES: biostudies-other