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

2014; American Association of Immunologists; Volume: 194; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.1402605

1550-6606

Maria Rosaria Bassi, Michael Kongsgaard, Maria Abildgaard Steffensen, Christina Fenger, Michael Rasmussen, Karsten Skjødt, Bente Finsen, Anette Stryhn, Søren Buus, Jan Pravsgaard Christensen, Allan Randrup Thomsen,

Cytomegalovirus and herpesvirus research

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.