A high probability of short-range interactions between fibrocytes and CD8+ T cells potentiates the inflammatory response in COPD

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 investigated whether tissue fibrocytes, can interact with CD8+ T cells, and if the contact between both cell types could be a cause of chronic immune activation. Using co-immunostaining of bronchial specimens, we showed that fibrocytes and CD8+ T cells are found in close proximity within distal airways and that, indirect and direct interactions are more frequent in tissues from COPD patients compared to those of control subjects. The interaction between both cell types was associated with lung function alteration. Transcriptomic analyses and functional experiments demonstrated that tissular CD8+ T cells from patients with COPD promoted fibrocyte chemotaxis via the CXCL2/8-CXCR1/2 axis. In an in vitro assay based on autologous co-culture with fibrocytes and CD8+ T cells isolated from COPD patients, individual CD8+ T cells established short-lived interactions with fibrocytes. Direct contacts between both cell types trigger CD8+ T cell proliferation in a CD54- and CD86-dependent manner, as well as cytokines production. From these results, we defined a computational model, with intercellular interactions, which fit to our experimental measurements. The modifications of the local interaction rules led to two cell distributions, depending on the subject considered as healthy or COPD. This study reveals that local interactions between fibrocytes and CD8+ T cells can occur in vivo and could jeopardize the balance between protective immunity and chronic inflammation in bronchi of COPD patients.