Recipients with higher percent predicted FEV1 early after lung transplantation have more circulating regulatory T cells

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 in lung transplant recipients. Clinically, the most valuable parameter of lung allograft function is the % predicted FEV1 measured in spirometry for diagnosis of both acute and chronic rejection. Stable high values may thus represent an immunologically favourable course. In this analysis, we present a cohort of 89 patients, in which we analyzed Tregs after lung transplantation as well as lung function results.

Materials and methods: In consecutive routine lung transplant recipients, the number of circulating Treg was measured by flow cytometry before transplantation and 3 weeks, 3 months, 6 months and 12 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 CTLA4, CD127 and FoxP3. Additionally, lung function results at the time points 3 weeks, 3 months, 6 months and 12 months after transplantation were analyzed. To divide the cohort into two groups based on the postoperative course of FEV1, a loss of 10% of FEV1 was defined as unfavourable course suggesting the possible development of rejection whereas a stable FEV1 was defined as stable postoperative development. From there, repeated measures ANOVA was performed monitoring the different surface molecules.

Results: A total of 89 consecutive patients were included into the study. Three weeks after transplantation we detected a statistically significant positive correlation between % predicted FEV1 and the number of CD4+CD25highCD127low T cells, constituting putative regulatory T cells (p < 0.05). More positive correlations were found between % predicted FEV1 and CD4+CD25highCTLA-4+ T cells (p < 0.05), total CD4+CD25high T cells (p < 0.05), and CD4+CD25highFoxP3+ T cells (p < 0.05).

Conclusions: The number of circulating putative Treg in peripheral blood may indicate a favourable immunologic course after lung transplantation resulting in better % predicted FEV1 in the first year after transplantation. Longterm follow up is necessary to predict BOS development, though.