High Circulating CD4+CD25hiFOXP3+ T Cell Subpopulation Early After Lung Transplantation is Associated with Development of Bronchiolitis Obliterans Syndrome

Purpose Despite treatment improvement, the bronchiolitis obliterans syndrome (BOS) affects more than 50% of the lung-transplant recipient in the 5 years post-transplantation and because it cannot be predict or cure, it is the major cause of death after lung transplantation (TP). The purpose of this study was to assess whether the peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients. Methods An in-depth profiling of CD4+ and CD8+ T cells was prospectively performed on blood cells from stable and BOS patients with a longitudinal follow-up. Samples were obtained and analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis, and at an intermediate time point at 6 to 12 months before BOS diagnosis. Results Whereas no significant difference was found for T cell compartments at BOS diagnosis or several months before, we report an increase in the CD4+CD25hiFoxP3+ T cell subpopulation in BOS patients at 1 and 6 months after transplantation (3.39%±0.40 vs 1.67%±0.22 in STA, P<0.001). A CD4+CD25hiFoxP3+ T cell threshold of 2.4% discriminated BOS and stable patients at 1 month post-transplantation. This was validated on a second set of patients at 6 months post-transplantation. Patients with a proportion of CD4+CD25hiFoxP3+ T cells up to 2.4% in the 6 months following transplantation had a 2 fold higher risk of developing BOS. Conclusion This study is the first to report an increased proportion of circulating CD4+CD25hiFoxP3+ T cells early post-transplantation in lung recipients who will develop BOS within 3 years, and document support for its use as a BOS predictive biomarker.