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DOI: 10.1055/s-0031-1295942
Downregulation of CD73 surface expression in regulatory as well as effector T cells in chronic HCV infection
Aims: Chronically persisting hepatitis C virus (HCV) infection is characterized by a dysfunctional cellular immune response. Here, we investigate the surface expression of CD39 (ectonucleosid triphosphat diphosphorylase), CD73 (5´-ectonucleotidase) and CD26 (dipeptidyl peptidase IV), that are believed to be important T cell differentiation markers and are highly expressed on murine regulatory T cells (Tregs). Together they convert extracellular ATP into ADP, AMP and eventually into adenosine (ADO). And they have an inhibitory effect on the cellular immune response.
Methods: PBMC of a cohort of 40 HCV patients were analyzed by multicolor flow cytometry to determine the extracellular bulk expression of CD39, CD73, CD26 as well as HLA-DR on Tregs (as defined FoxP3+, CD25high) and CD4+ and CD8+ T cells. For a subset of patients liver biopsies were available. Furthermore, functional assays were performed with live-sorted cells to analyze the cytokine profile.
Results: We found a significant increase of the Treg frequency in chronically infected HCV patients. There were only small differences of CD39 and CD26 expression between healthy subjects and HCV patients in all T cell subsets. Surprisingly, CD73 was generally only expressed in a small subset of Tregs in healthy subjects. Most importantly, all T cell subsets (Tregs, CD4+, CD8+ including intrahepatic T cells) show a significant down-regulation of CD73 in HCV infection. This downregulation was most marked in CD8+ T cells where it correlated with the activation status/HLA-DR expression (p=0.02). First results of the functional analysis show that sorted CD73- T CD8+ cells produce more IFN γ and less IL–2 than their CD73+ counterparts. (p<0.01).
Summary: There is a general down regulation of T cell CD73 expression in HCV Infection. Further studies are needed to investigate whether CD73 down-regulation is a mere sign of cellular activation and investigate the exact role of CD73 in HCV infection.