Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells
- 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.
Author: | Verena Schlaphoff, Sebastian Lunemann, Pothakamuri Venkata Suneetha, Jerzy Jaroszewicz, Jan Grabowski, Julia DietzORCiDGND, Fabian Arnold HelfritzORCiDGND, Hueseyin Bektas, Christoph SarrazinGND, Michael P. MannsORCiDGND, Markus CornbergORCiDGND, Heiner WedemeyerORCiDGND |
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URN: | urn:nbn:de:hebis:30-114233 |
DOI: | https://doi.org/10.1371/journal.ppat.1002045 |
ISSN: | 1553-7374 |
Parent Title (English): | PLoS pathogens |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2011/05/19 |
Date of first Publication: | 2011/05/19 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2011/09/01 |
Volume: | 7 |
Issue: | (5): e1002045 |
Page Number: | 14 |
First Page: | 1 |
Last Page: | 14 |
Note: | Copyright: © 2011 Schlaphoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
HeBIS-PPN: | 275127850 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Sondersammelgebiets-Volltexte | |
Licence (German): | Creative Commons - Namensnennung 3.0 |