Short-range interactions between fibrocytes and CD8⁺ T cells in COPD bronchial inflammatory response

Abstract

The peri-bronchial zone of chronic obstructive pulmonary disease (COPD) is the site of extensive infiltration of immune cell, allowing persistent contacts between resident cells and immune cells. Tissue fibrocytes interaction with CD8⁺ T cells and its consequences were investigated. We show that fibrocytes and CD8⁺ T cells are found in vicinity in distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8+ T cells and fibrocytes are associated with altered lung function. Tissular CD8⁺ T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. CD8⁺ T cells establish short-term interactions with fibrocytes, that trigger CD8+ T cell proliferation in a CD54− and CD86-dependent manner, as well as pro-inflammatory cytokines production. We defined a computational model, with intercellular interactions fitting to our experimental measurements. This model allowed not only to accurately predicts histological ex vivo characteristics but also to monitors disease evolution. 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.