Adoptive transfer of hepatocyte growth factor transfected T cells in a bleomycin injured murine lung model

Introduction: After decades of looking into potential related mechanisms, idiopathic pulmonary fibrosis (IPF) remains a lethal disease. The role of pulmonary immune cells, especially regulatory T cells (Treg), is still not yet well understood. IPF is accepted as a disease following alveolar epithelial integrity disruption due to aberrant wound repair mechanisms. Recent studies pointed the beneficial effect of the hepatocyte growth factor (HGF) towards alveolar epithelial recovery. In this study, we test if adoptive transfer of HGF expressing T cells could induce alveolar epithelial repair by restoring immune cell homeostasis in the murine lung in a bleomycin lung injury model. Methods: Mice were sacrificed on days 7, 10 and 14 following bleomycin instillation (1.52U/kg). Single cell suspensions of lung parenchyma (LP), bronchoalveolar lavage fluid (BALF) and lung draining lymph nodes (LDLN) were analyzed by flow cytometry to study immune cell homeostasis. Adoptive transfer of 5x105 HGF-transfected CD3+ T cells was performed 7 days after bleomycin instillation and mice were sacrificed 7 days following administration. Results: We observed increased frequencies in Tregs and CD8+T cells as well as macrophages and dendritic cells in LP after HGF transfected and non-transfected T cell administration in comparison to mice treated with bleomycin only. Similar patterns of change in frequencies of Treg, CD8+, macrophages and dendritic cells were observed in LDLN. Conclusion: Adoptive T cell therapy showed clear alteration of pulmonary immune cell subsets frequencies during the course of bleomycin induced lung injury. We need to pursue further investigations in order to determine its potential therapeutic role in restoration of immune cell homeostasis during course of human IPF.