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CD8+ T cells complement antibodies in protecting against yellow fever virus.
J Immunol. 2015 Feb 01; 194(3):1141-53.JI

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.

Authors+Show Affiliations

Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark; and.Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of Cancer and Inflammation, Institute for Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark.Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark; and.Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; athomsen@sund.ku.dk.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25539816

Citation

Bassi, Maria R., et al. "CD8+ T Cells Complement Antibodies in Protecting Against Yellow Fever Virus." Journal of Immunology (Baltimore, Md. : 1950), vol. 194, no. 3, 2015, pp. 1141-53.
Bassi MR, Kongsgaard M, Steffensen MA, et al. CD8+ T cells complement antibodies in protecting against yellow fever virus. J Immunol. 2015;194(3):1141-53.
Bassi, M. R., Kongsgaard, M., Steffensen, M. A., Fenger, C., Rasmussen, M., Skjødt, K., Finsen, B., Stryhn, A., Buus, S., Christensen, J. P., & Thomsen, A. R. (2015). CD8+ T cells complement antibodies in protecting against yellow fever virus. Journal of Immunology (Baltimore, Md. : 1950), 194(3), 1141-53. https://doi.org/10.4049/jimmunol.1402605
Bassi MR, et al. CD8+ T Cells Complement Antibodies in Protecting Against Yellow Fever Virus. J Immunol. 2015 Feb 1;194(3):1141-53. PubMed PMID: 25539816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 - Stryhn,Anette, AU - Buus,Søren, AU - Christensen,Jan P, AU - Thomsen,Allan R, Y1 - 2014/12/24/ PY - 2014/12/26/entrez PY - 2014/12/30/pubmed PY - 2015/4/15/medline SP - 1141 EP - 53 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 194 IS - 3 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/25539816/CD8+_T_cells_complement_antibodies_in_protecting_against_yellow_fever_virus_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=25539816 DB - PRIME DP - Unbound Medicine ER -