CD8+ T Cells Complement Antibodies in Protecting against Yellow Fever Virus

Maria R Bassi; Michael Kongsgaard; Maria A Steffensen; Christina Fenger; Michael Rasmussen; Karsten Skjødt; Bente Finsen; Anette Stryhn Buus; Søren Buus; Jan P Christensen; Allan Randrup Thomsen

doi:10.4049/jimmunol.1402605

CD8⁺ T Cells Complement Antibodies in Protecting against Yellow Fever Virus

Maria R Bassi, Michael Kongsgaard, Maria A Steffensen, Christina Fenger, Michael Rasmussen, Karsten Skjødt, Bente Finsen, Anette Stryhn Buus, Søren Buus, Jan P Christensen, Allan Randrup Thomsen

40 Citations (Scopus)

Abstract

The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.

Original language	English
Journal	Journal of immunology (Baltimore, Md. : 1950)
Volume	194
Issue number	3
Pages (from-to)	1141-53
Number of pages	13
ISSN	0022-1767
DOIs	https://doi.org/10.4049/jimmunol.1402605
Publication status	Published - 1 Feb 2015

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title = "CD8+ T Cells Complement Antibodies in Protecting against Yellow Fever Virus",

abstract = "The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.",

author = "Bassi, {Maria R} and Michael Kongsgaard and Steffensen, {Maria A} and Christina Fenger and Michael Rasmussen and Karsten Skj{\o}dt and Bente Finsen and Buus, {Anette Stryhn} and S{\o}ren Buus and Christensen, {Jan P} and Thomsen, {Allan Randrup}",

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T1 - CD8+ T Cells Complement Antibodies in Protecting against Yellow Fever Virus

AU - Bassi, Maria R

AU - Kongsgaard, Michael

AU - Steffensen, Maria A

AU - Fenger, Christina

AU - Rasmussen, Michael

AU - Skjødt, Karsten

AU - Finsen, Bente

AU - Buus, Anette Stryhn

AU - Buus, Søren

AU - Christensen, Jan P

AU - Thomsen, Allan Randrup

PY - 2015/2/1

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N2 - The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.

AB - The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.

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