The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education
NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo mo...
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| Published in: | The Journal of immunology (1950) Vol. 195; no. 7; p. 3262 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.10.2015
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| ISSN: | 1550-6606, 1550-6606 |
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| Abstract | NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education. |
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| AbstractList | NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education. NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education.NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education. |
| Author | Blom, Kim Braun, Monika Falconer, Karolin Fogdell-Hahn, Anna Michaëlsson, Jakob Ivarsson, Martin A Sandberg, Johan K Marquardt, Nicole Gustafsson, Rasmus Gonzalez, Veronica D |
| Author_xml | – sequence: 1 givenname: Nicole surname: Marquardt fullname: Marquardt, Nicole organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 2 givenname: Martin A surname: Ivarsson fullname: Ivarsson, Martin A organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 3 givenname: Kim surname: Blom fullname: Blom, Kim organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 4 givenname: Veronica D surname: Gonzalez fullname: Gonzalez, Veronica D organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 5 givenname: Monika surname: Braun fullname: Braun, Monika organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 6 givenname: Karolin surname: Falconer fullname: Falconer, Karolin organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 7 givenname: Rasmus surname: Gustafsson fullname: Gustafsson, Rasmus organization: Department of Clinical Neuroscience, Multiple Sclerosis Research Group, Center for Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden – sequence: 8 givenname: Anna surname: Fogdell-Hahn fullname: Fogdell-Hahn, Anna organization: Department of Clinical Neuroscience, Multiple Sclerosis Research Group, Center for Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden – sequence: 9 givenname: Johan K surname: Sandberg fullname: Sandberg, Johan K organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and – sequence: 10 givenname: Jakob surname: Michaëlsson fullname: Michaëlsson, Jakob email: jakob.michaelsson@ki.se organization: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and jakob.michaelsson@ki.se |
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| Copyright | Copyright © 2015 by The American Association of Immunologists, Inc. |
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| SubjectTerms | Adult Antibodies, Neutralizing - immunology Antigens, CD - biosynthesis Antigens, Differentiation, T-Lymphocyte - biosynthesis B-Lymphocytes - immunology CD57 Antigens - metabolism Cell Differentiation - immunology Cell Proliferation Histocompatibility Antigens Class I - immunology Humans Interferon Type I - blood Interferon Type I - immunology Interleukin-12 Subunit p35 - immunology Interleukin-18 - immunology K562 Cells Ki-67 Antigen - biosynthesis Killer Cells, Natural - cytology Killer Cells, Natural - immunology Lectins, C-Type - biosynthesis Lymphocyte Activation - immunology Middle Aged Receptors, KIR - immunology T-Lymphocytes - immunology Vaccines, Attenuated - immunology Viral Load - immunology Viral Vaccines - immunology Yellow Fever Vaccine - immunology Yellow fever virus - immunology |
| Title | The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education |
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