Developing a score of early postoperative regulatory T cell frequency to predict bronchiolitis obliterans syndrome-free survival at two years after lung transplantation

Introduction: Regulatory T cells (Treg) have potential to regulate alloantigens and thus may counteract the development of chronic rejection (i.e. bronchiolitis obliterans syndrome, BOS) in lung transplantation. BOS may affect over 60% of lung transplant recipients within five years. Here, we analyzed Tregs in peripheral blood of 120 lung recipients prospectively during the first 2 years and correlated with the onset of BOS at two years. Materials and Methods: In this study we detected circulating Treg by flow cytrometry in consecutive routine lung transplant recipients before transplantation 3 weeks, 3, 6, 12, 18 and 24 months after transplantation. Treg were defined as CD4+CD25high T cells and were further analyzed for relevant surface as well as intracellular markers such as, amongst others, CTLA4, CD127, FoxP3 and IL-2. Spirometry at 3 weeks, 3, 6, 12, 18 and 24 months after transplantation as well as protocol biopsy results were analyzed. We defined two groups by the development of BOS stage 1 or higher versus BOS stage 0 at two years. Results: A total of 120 consecutive patients were included into the study. While 97 patients showed a stable clinical course after lung transplantation, 23 patients developed BOS stage 1 or higher within the first 2 years after lung transplantation. As soon as 3 weeks after lung transplantation not only a statistically significant positive correlation could be detected between the frequencies of Tregs and the absence of BOS (p < 0.05), we also built a score defining a cut off value composed of IL2+/CTLA4+/CD127low and FoxP3+ Treg in peripheral blood at 3 weeks, predicting the probability of BOS development. Conclusions: Higher frequencies of Treg early after lung transplantation are associated with protection against development of BOS and they may thus have an early predictive function for the ensuing course following transplantation.