Z Gastroenterol 2011; 49 - P4_40
DOI: 10.1055/s-0030-1269695

The association of 2B4 up-regulation and SAP down-regulation indicates exhaustion of virus-specific CD8+ T cells

V Schlaphoff 1, S Lunemann 1, SV Pothakamuri 1, J Jaroszewicz 1, J Grabowski 1, S Pischke 1, FA Helfritz 2, MP Manns 3, M Cornberg 4, H Wedemeyer 5
  • 1Abt. Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
  • 2Abt. Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover
  • 3Medical High School, Hannover
  • 4Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
  • 5Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie, Hannover

The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection.We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD-1 blockade. In conclusion, we suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.

2B4 - CD8+ T cells - PD-1 - hepatitis C