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

Autor: Verena Schlaphoff, Sebastian Lunemann, Pothakamuri Venkata Suneetha, Jerzy Jaroszewicz, Jan Grabowski, Julia Dietz, Fabian Helfritz, Hueseyin Bektas, Christoph Sarrazin, Michael Peter Manns, Markus Cornberg, Heiner Wedemeyer
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS Pathogens, Vol 7, Iss 5, p e1002045 (2011)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1002045
Popis: 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.
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