A high probability of short-range interactions between fibrocytes and CD8+ T cells potentiates the inflammatory response in COPD - 17/02/23

Peri-bronchial area of COPD are the siege of extensive immune cell infiltration and tissue remodelling, 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 undue 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. Transcriptomic analyses and functional experiments were used to invastigate tissular CD8⁺ T cells capacity to attract fibrocytes. Direct and indirect autologous 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 fitting to our experimental measurements.

We show that fibrocytes and CD8⁺ T cells are found in vicinity in distal airways and that interactions (both indirect and direct) are more frequent in tissues from COPD patients compared to those of control subjects. Increased interactions between CD8⁺ T cells and fibrocytes are associated with altered lung function. We demonstrated that tissular CD8⁺ T cells from COPD patients promote fibrocyte chemotaxis via the CXCL2/8-CXCR1/2 axis. In an in vitro assay, 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 pro-inflammatory cytokines production. Computer modelling allowed not only to accurately describe cellular distribution depending on whether the subject is healthy or COPD but also to follow the dynamics and predict responses to therapeutic agents.

Altogether, our 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.