Short-range interactions between fibrocytes and CD8+ T cells modulate the balance between tissue repair and destruction in COPD

Abstract

Bronchi from COPD are an area of extensive immune cell infiltration and changes in tissue structures, allowing persistent contacts between resident and immune cells. We investigate whether tissue fibrocytes, recently evidenced around COPD bronchi lung, can interact with CD8+ T cells, and whether the contact between both cell types could alter the balance between tissue repair and destruction. Using co-immunostaining of bronchial specimens, we show that fibrocytes and CD8+ T cells are found within close proximity in distal airways of COPD patients, and that indirect and direct interactions are more frequent in tissue from COPD patients compared to those of control subjects. The density of interacting cells is negatively associated with lung function parameters, such as FEV1/FVC. Transcriptome analysis and functional experiments indicate that the attractive capacity of tissular CD8+ T cells is greater in COPD patients than in control subjects. Using in vitro assay based on autologous co-culture with fibrocytes and CD8+ T cells isolated from blood samples of COPD patients, we demonstrate that direct contact between both cell types trigger CD8+ T cell proliferation, and IFN-ɣ, TNF-α and granzyme B production. From these results, we defined a stochastic and computational model, based on local intercellular interactions, with the objective to predict the distributions of the two cell types, depending on whether the subject is healthy or COPD. Altogether, this study reveals that local intercellular interactions between fibrocytes and CD8+ T cells can occur in vivo and could result in increased proliferation of CD8+ T cells in the bronchi of COPD patients.