TY - JOUR T1 - Dual Function of the NK Cell Receptor 2B4 (CD244) in the Regulation of HCV-Specific CD8+ T Cells A1 - Schlaphoff, Verena A1 - Lunemann, Sebastian A1 - Suneetha, Pothakamuri Venkata A1 - Jaroszewicz, Jerzy A1 - Grabowski, Jan A1 - Dietz, Julia A1 - Helfritz, Fabian A1 - Bektas, Hueseyin A1 - Sarrazin, Christoph A1 - Manns, Michael Peter A1 - Cornberg, Markus A1 - Wedemeyer, Heiner Y1 - 2011/05/19 N2 - Author Summary Infection with the hepatitis C Virus (HCV) is a world-wide health burden, the infection becomes persistent in the majority of cases. In chronic patients HCV-specific immune responses are weak, HCV-specific CD8+ T cells were shown to be functionally exhausted and to be negatively controlled by costimulatory molecules like PD-1. Here, we show that the costimulatory molecule 2B4 (CD244) is also involved in the regulation of HCV-specific CD8+ T cell responses and that 2B4 expression is selectively upregulated on virus-specific CD8+ T cells in persistent infections. Proliferation of HCV-specific CD8+ T cells from chronic patients increased by 2B4 cross-linking only if the ex vivo 2B4 expression was low, while we could observe no effect on samples with high 2B4 expression levels. Of note, expression of the intracellular 2B4 adaptor molecule SAP, which leads to an activation of the cell, decreased with higher 2B4 expression levels. Finally, we were able to show that 2B4 cross-linking can counter-act enhanced proliferation of HCV-specific CD8+ T cells seen upon PD-1 blockade. Thus, our study provides new insights into the regulation of CD8+ T cell responses demonstrating an implication of the costimulatory molecule 2B4. JF - PLOS Pathogens JA - PLOS Pathogens VL - 7 IS - 5 UR - https://doi.org/10.1371/journal.ppat.1002045 SP - e1002045 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1002045 ER -