Late Breaking Abstract - Peripheral T-cells and their cytokine production in Chronic Thromboembolic Pulmonary Hypertension

Background: Accumulating evidence shows involvement of the immune system in CTEPH pathogenesis. Previous studies have shown increased presence of T-cells and chemokines in CTEPH surgical PEA material. Currently, no data is present for further determination and classification of these T-cells. Moreover, no data are available regarding T-cell activation, cytokine production, and Th-subset division in treatment naïve CTEPH patients. Therefore, our aim was to more closely investigate peripheral blood T cells in CTEPH patients at diagnosis. Methods: Peripheral blood samples were collected from 43 CTEPH patients at baseline and 17 healthy controls (HC). Th-subset division, T-cell activation, and cytokine production were measured in CTEPH patients at diagnosis and compared to HC. Results: At baseline, we found increased proportions of CCR6+ CD4+ CD45RA- T-cells compared to HC. CD4+ CD45RA- T-cells of CTEPH patients showed decreased cytokine production. Strikingly, we found increased CTLA4 expression on CD4+ T cells, indicating a regulatory or immunomodulatory effect. After unsupervised clustering analysis for these T cell subsets and activation markers, CTEPH patients were clustered separately from HCs due to CTLA4 expression and CCR6+ cells. No specific changes were found for central vs peripheral thrombotic lesions at baseline within CTEPH patients. Conclusion: Taken together, we found evidence for CCR6+ CD4+ T cell-dependent changes in peripheral blood samples in CTEPH patients. We found decreased cytokine production in CD45RA- CD4+ T-cells, indicating suppression or exhaustion. Overall, our studies indicate a possible role for CCR6+ T cell-dependent immunopathology in CTEPH patients.