Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease with chronic inflammation, in which CD8+ T cells play a key role. Since circulating and tissue fibrocytes are associated with mortality and bronchial obstruction, respectively, we investigated whether tissue fibrocytes can interact with CD8+ T cells, and whether the contact between both cell types could be a cause of chronic immune activation.
Using co-immunostaining of bronchial specimens obtained from surgery in 17 COPD patients and 25 control subjects, and specific image analysis methods, we quantified the relative distribution of fibrocytes and CD8+ T cells. Direct and indirect co-cultures of fibrocytes and CD8+ T cells, isolated from blood samples of COPD patients, were performed to test fibrocyte effect on CD8+ T cell proliferation and cytokines secretion profile. We defined a computational model with intercellular interactions which fits to experimental measurements and explains the macroscopic properties of cell populations in situ.
The density of fibrocytes in contact with CD8+ T cells and the minimal distance between both cell types were respectively higher and lower in tissue specimens from COPD patients compared with those of control subjects. We also demonstrated that direct contact between both cell types triggered in vitro naïve and memory CD8+ T cell differential proliferation and IFN-ɣ and TNF-α production. Computer modelling predicted that modification in local intercellular interactions induced changes in cell repartitions similar to those measured in situ.
This study reveals that direct intercellular interactions between fibrocytes and CD8+ T cells can occur in vivo and could potentiate the inflammatory response in lungs from COPD patients.Le texte complet de cet article est disponible en PDF.
Keyword : COPD