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Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells

By Verena Schlaphoff, Sebastian Lunemann, Pothakamuri Venkata Suneetha, Jerzy Jaroszewicz, Jan Grabowski, Julia Dietz, Fabian Arnold Helfritz, Hueseyin Bektas, Christoph Sarrazin, Michael P. Manns, Markus Cornberg and Heiner Wedemeyer

Abstract

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 PD1 blockade. 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

Topics: ddc:570
Year: 2011
OAI identifier: oai:publikationen.ub.uni-frankfurt.de:22568

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