Characterization of unique pro-fibrotic T cells resident in the lungs

Background: Lung fibrosis is characterized by excessive collagen deposition in the extracellular matrix that leads to destruction of lung architecture, and there is a need for novel therapeutic approaches for patients with lung fibrosis. Aim: We hypothesized that T cells in the lung may play a key part in the fibrotic process. We therefore investigated the cytokine secretion profile and clonal relationship of lung CD4 T cells in patients with lung fibrosis. Methods: BAL and peripheral blood were obtained from 25 patients (aged 59-75) diagnosed with idiopathic pulmonary fibrosis, non-classifiable lung fibrosis and hypersensitivity pneumonitis (non-CTD lung fibrosis) and 11 patients (aged 29-66) diagnosed with CTD (connective tissue disease) lung fibrosis. T cells from BAL and blood were stimulated in vitro (3.5h) for cytokine characterization (all samples) and T cell receptor (TCR) of single T cells was sequenced for clonality analysis (n=4). Results: The cytokine production capacity CD4 T cells from fibrosis patients revealed a unique expression of the profibrotic cytokine IL-13 in combination with the cytokine IFNγ in BAL but not in blood. In patients with non-CTD lung fibrosis these unique BAL cells constituted 13% of the CD4 T cells and only 3% in patients with CTD lung fibrosis (p Conclusion: Non-CTD lung fibrosis contains an unusual population of CD4+ T cells producing profibrotic IL-13 together with proinflammatory IFNγ in BAL but not in blood. Such cells are clonally expanded, thus indicating local proliferation by antigens present in the lung.