Bronchiolitis Obliterans Syndrome-Free Survival after Two Years in Patients with Higher Frequencies of Regulatory T Cells Early after Lung Transplantation

Abstract

Purpose Regulatory T cells (Treg) play important roles in the induction and maintenance of immunological tolerance to self and non-self antigens. They have the potential to regulate alloantigens and thus may counteract the development of acute and chronic rejection (i.e. BOS) in lung transplant recipients. BOS affects over 60% of lung transplant recipients within 5 years after transplantation. Here, we present a cohort of 89 patients, in which we analyzed Tregs in peripheral blood prospectively during the first 2 years after lung transplantation and correlate with the onset of BOS. Methods and Materials In consecutive routine lung transplant recipients, the number of circulating Treg was detected by flow cytometry before transplantation and 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. Additionally, lung function results at that time points were analyzed. We divided the cohort into two groups based on the development of BOS stage 0-p versus BOS stage 1 or higher. Results A total of 89 consecutive patients were included into the study. 25 patients developed a BOS stage 1 or higher 2 years after transplant. 64 patients showed a good clinical course with stable lung function. A statistically significant positive correlation could be detected between the frequencies of CD4+CD25highCD127low T cells, CD4+CD25highCTLA-4+ T cells, CD4+CD25highFoxP3+ T cells and CD4+CD25highIL-2 + T cells and the absence of BOS within the first 2 years after lung transplantation (p 0.05). Conclusions Higher frequencies of CD4+CD25highCD127low T cells, CD4+CD25highCTLA-4+ T cells, CD4+CD25highFoxP3+ T cells and CD4+CD25highIL-2 + T cells early after transplantation are associated with protection against development of BOS during the initial 2 years after lung transplantation.