Z Gastroenterol 2012; 50 - P4_56
DOI: 10.1055/s-0031-1295942

Downregulation of CD73 surface expression in regulatory as well as effector T cells in chronic HCV infection

I Tóth 1, AQ Le 2, P Hartjen 1, A Thomssen 3, C Beisel 4, C Scheurich 1, V Matzat 4, S Kummer 1, S Polywka 5, C Frenzel 4, AW Lohse 4, S Lüth 4, J van Lunzen 6, J Schulze zur Wiesch 4
  • 1Heinrich Pette Institut - Leibniz Institut für Experimentelle Virologie (HPI), Hamburg
  • 2Simon Fraser University, Burnaby, BC, Kanada
  • 3Department of General Surgery, University Medical Center Hamburg-Eppendorf, Hamburg
  • 4I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • 5Medizinische Mikrobiologie, Universitätsklinikum Hamburg Eppendorf, Hamburg
  • 6Ambulanzzentrum für Infektiologie, Universitätsklinikum Hamburg – Eppendorf, Hamburg

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.