T-cell pathways in lung tissue of patients with advanced COPD and IPF requiring lung transplantation

Abstract

Introduction: Lymphocytes T have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), but their role in advanced disease is not fully explained and remains controversial. Aims: The aim of our study was to investigate subsets of lung tissue lymphocytes T in advanced COPD and IPF patients undergoing transplantation and compare them to healthy lung tissue from donors, who were used as controls. Methods: Lung tissue was obtained from 9 patients with COPD and 9 patients with IPF as well as 7 donor patients. The tissue lymphocytes (Th1, Th2, Th17, Treg, activation markers and differentiation of CD8 cells) were analyzed with flow cytometry and the expression of transcription factors was analyzed by qPCR. Results: The most prominent finding was more than 20-fold increase of Th1 cells in COPD and IPF compared to healthy controls (median 6.8% (IQR 2.7-15.5) and 6.9% (4.2-10,2) respectively vs. 0.28% (0.12-1.06) of lymphocytes, p 0,001). Flow cytometric differences in Th1 were confirmed with upregulation of TBET1 transcription factors. Furthermore, in COPD and IPF patients all CD8 T cell were fully differentiated cytotoxic phenotype (more than 98.7%). The proportions of those cells were also markedly increased (median 12.6% (8.9-22.6) and 15.2% (9.6-27.6) respectively vs. 2.3% (1.0-10.8) of lymphocytes, p 0.013). Conclusions: Our results indicate that the inflammation in advanced COPD and IPF predominantly involves Th1 lymphocytes and CD8+ lymphocytes with the greatest cytotoxic potential. Importantly, in COPD and IPF at a final stage of disease the exaggerated inflammation pattern seems to be highly comparable.