Expression of PD-1/PD-L1 axis and CD4/CD8 ratio in mediastinal lymph nodes of human and experimental lung fibrosis

Abstract

<b>Introduction:</b> Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. <b>Aim:</b> To compare lymphocyte expression of PD-1/PD-L1 axis and CD4/CD8 ratio in mediastinal lymph nodes of patients with IPF and lung cancer. To measure PD-1 and PD-L1 mRNA expression as well as CD4/CD8 ratio following bleomycin induced pulmonary fibrosis. <b>Methods:</b> Lymph node sampling was performed through endobronchial ultrasound (EBUS) bronchoscopy. The percentage of PD-1/PD-L1 positive and CD4/CD8 lymphocytes was measured. PD-1, PD-L1 mRNA expression and CD4/CD8 ratio were measured in&nbsp;tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. <b>Results:</b> Thirty two patients (n=32) were included (IPF: n=13, lung cancer: n=10, concomitant IPF and lung cancer: n=9). Median PD-1% expression and CD4/CD8 ratio were higher in lymphocytes of patients with IPF compared to lung cancer.&nbsp;Tracheobronchial lymph nodes isolated from bleomycin-treated mice exhibited increased PD-1 and PD-L1 mRNA levels, as well as increased CD4/CD8 ratio compared to saline-treated mice. Accordingly, percentage of CD4+/PD-1+ out of CD45+ cells was higher in bleomycin-treated mice than saline-treated mice. <b>Conclusion:</b> Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles of lymphocyte subpopulations than patients with lung cancer. Mediastinal lymph nodes of mice enlarge and express different lymphocyte subpopulations following bleomycin administration. PD-1+CD4+ T cells might be a therapeutic target in pulmonary fibrosis.