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.
Vyšlo v časopise:
Dual Function of the NK Cell Receptor 2B4 (CD244) in the Regulation
of HCV-Specific CD8+ T Cells. PLoS Pathog 7(5): e32767. doi:10.1371/journal.ppat.1002045
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002045
Souhrn
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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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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