Human T cells stimulate fibroblast‐mediated degradation of extracellular matrix in vitro

Several chronic diseases are characterized by inflammation, T cell recruitment and tissue remodelling. We hypothesized that activated T cells may stimulate remodelling of extracellular matrix (ECM) in vitro. Total T cells (CD3+) as well as CD4+ and CD8+ subsets were isolated from peripheral blood and stimulated, after which conditioned media (CM) were obtained. CM was added to human lung fibroblasts in three‐dimensional collagen gels and the area of gels was measured daily. Hydroxyproline was determined as a measure of collagen degradation in the gels. Matrix metalloproteinase (MMP) activity in the culture media was analysed by gelatine zymography. Cytokine secretion of stimulated CD4+ and CD8+ T cells was analysed. CD3+ CM augmented collagen gel contraction in a time‐ and dose‐dependent manner (P < 0·0001). CD4+ T cell CM was more potent than CD8+ T cell CM (P < 0·001). CD3+ CM and CD4+ T cell CM, but not CD8+ T cell CM, stimulated fibroblast‐mediated collagen degradation and MMP‐9 activity. A broad‐spectrum MMP‐inhibitor added to the culture system inhibited both gel contraction and MMP activity. Activated CD4+ T cells secreted significantly more tumour necrosis factor (TNF) and interleukin (IL)‐6 compared to CD8+ T cells. CD3+ CM from patients with chronic obstructive pulmonary disease stimulated fibroblast‐mediated collagen gel contraction to the same magnitude as CD3+ CM from healthy controls. In conclusion, activated CD4+ T cells can stimulate fibroblast‐mediated degradation of ECM in vitro. This could be a mechanism by which activated T cells stimulate degradation of lung tissue leading to pulmonary emphysema.

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