Regulatory T Cells Correlate with Percent Predicted FEV1 after Lung Transplantation

Abstract

Purpose: Regulatory T cells (Treg) possibly contribute significantly to allograft survival and may counteract the development of BOS in lung transplant patients. Clinically, the most valuable parameter of lung allograft function is the %predicted FEV1 measured in spirometry. It is used for diagnosis of both acute and chronic rejection episodes and 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. Methods and Materials: In all patients, the number of circulating Tregs was measured by flow cytometry 3 weeks as well as 3 months, 6 months and 12 months after transplantation. Putative Treg were defined as CD4+CD25high T cells and were further analyzed for different surface as well as intracellular molecules such as CD152, CD127 as well as FoxP3. Additionally, lung function results at the time points 3 weeks, 3 months, 6 months and 12 months after transplantation were analyzed. After performing a Spearmans test of correlation, the cohort was divided into two groups based on the postoperative course of FEV1. A loss of 10% of FEV1 defining an unfavourable course implying the development of BOS whereas a stable FEV1 was defined as stable postoperative development. With these two groups, a repeated measure ANOVA test was performed monitoring the different surface molecules. Results: A total of 89 patients were included into the study. The Spearmans test of correlation revealed a statistically significant correlation between the %predicted FEV1 measured 3 weeks after transplantation and the number of CD127low Treg (p< 0.05). Similar results were detectable between %predicted FEV1 at 3 months postoperatively and CD152+ (CTLA-4) Treg (p< 0.05) as well as CD4+CD25+ Treg and %predicted FEV1 6 months postoperatively (p< 0.05). Repeated measure ANOVA test revealed a statistically significant result relating the clinical course in the first postoperative year - defined by the course of %predicted FEV1- to the number of FoxP3+ Treg circulating in the peripheral blood (p< 0.05). Conclusions: The number of circulating Treg in the peripheral blood may indicate a favourable immunologic course after lung transplantation resulting in better %predicted FEV1 in the first year after transplantation.