Myeloid-Derived Suppressor Cells in Lung Transplant Recipients

Abstract

Purpose Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells of the myeloid lineage. MDSC expand in pathological situations such as chronic infections, cancer and transplant rejection; and suppress T-cell responses. Chronic lung allograft dysfunction (CLAD) is the single most important factor limiting long-term survival after lung transplantation (LTx), MDSCs may also play a role in its complex pathophysiology. We investigated the technical feasibility of quantifying granulocytic/polymorphonuclear MDSCs (G/PMN-MDSC) in peripheral blood from LTx recipients and secondly, assessed MDSC in post-transplant complications as infection and CLAD. Methods Peripheral blood was collected from healthy control subjects and LTx recipients in EDTA tubes at the University Hospitals Leuven (Belgium). Samples were shipped to Tubingen (Germany) on ice and analyzed the same day. Healthy control subjects (n=4) and lung transplant recipients (n=21: stable n=6, infection n=6, BOS n=5, RAS n=4) were included. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and MDSCs by Ficoll density gradient centrifugation. MDSC typing and counting was performed by flow cytometry to assess the percentage of G-MDSCs (CD11b+CD33b+CD66b+). Results G-MDSC were increased in stable LTx recipients (52.1 (33.3-61.9)%) versus healthy control subjects (9.4 (7.6-16.4)%) (p=0.0095). LTx recipients with an infection or CLAD had or tended to have lower % G-MDSC versus stable LTx recipients, respectively 28.2 (17.2-36.6)% (p=0.041) and 33.0 (25.6-38.1)% (p=0.088). Within CLAD % G-MDSC were comparable in BOS and RAS. Conclusion Circulating G-MDSCs are measurable in LTx recipients. Stable LTx recipients showed higher percentages of G-MDSCs, which decreased in post-transplant complications. These results invite for more in depth analysis of the role of MDSC after LTx.