Abstract
Traditionally, NK cells belong to the innate immune system and eliminate virus-infected cells through their germline-encoded receptors. However, NK cells were recently reported to possess memory-like functions that were predominantly provided by hepatic NK cells. Memory properties were mainly documented in contact hypersensitivity models or during cytomegalovirus infections. However, the precise role and the physiologic importance of memory-like NK cells during retroviral infections are still under investigation. Here, we show that Friend retrovirus (FV) infection of mice induced a population of phenotypically memory-like NK cells at 28 days post infection. Upon secondary antigen encounter, these NK cells showed an increased production of the pro-inflammatory cytokines IFNγ and TNFα as well as the death ligand FasL in comparison to naïve NK cells. Furthermore, we found an augmented elimination of antigen-matched but not antigen-mismatched target cells by these memory-like NK cells. In adoptive cell transfer experiments, equal antiviral activities of splenic and hepatic memory-like NK cells during the late phase of acute FV infection were found. Our results strongly imply the existence and antiviral activity of spleen and liver memory-like NK cells in FV infection, which efficiently respond upon secondary exposure to retroviral antigens.
Highlights
Natural killer (NK) cells classically belong to the innate immune system and fight cancers as well as intracellular pathogens
To address the question whether we can see an influx of NK cells into the peritoneum of naïve and previously Friend retrovirus (FV)-infected mice from the spleen and liver after FBL-3 challenge, we analyzed the absolute numbers of NK cells at 0, 6, Fig. 2 Cytotoxic functions of adaptive NK cells after challenge with FV-induced target cells
There were no differences in the percentage of F asL+ NK cells, we detected a significant increase of the mean fluorescence intensity (MFI) of FasL expression (Fig. 2d, Additional file 2: Fig. S2)
Summary
Natural killer (NK) cells classically belong to the innate immune system and fight cancers as well as intracellular pathogens. FV-infected mice with FV-derived tumor cells (FBL-3 cells expressing FV antigens) at 26 dpi (Fig. 2a). To address the question whether we can see an influx of NK cells into the peritoneum of naïve and previously FV-infected mice from the spleen and liver after FBL-3 challenge, we analyzed the absolute numbers of NK cells at 0, 6, Fig. 2 Cytotoxic functions of adaptive NK cells after challenge with FV-induced target cells.
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