PloS one · 2014
Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection.
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Verstrepen Babs E, Verschoor Ernst J, Fagrouch Zahra C, Mooij Petra, de Groot Natasja G, Bontrop Ronald E, Bogers Willy M, Heeney Jonathan L, Koopman Gerrit
Аннотация
A single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while the other three became chronically infected. In the animal that cleared infection, NS3-specific CD8 T-cell responses were observed to be more potent in terms of frequency and polyfunctionality of cytokine producing cells. Unique to this animal was the presence of killing-competent CD8 T-cells, specific for NS3 1258-1272, being presented by the chimpanzee MHC class I molecule Patr-A*03∶01, and a high affinity recognition of this epitope. In the animals that became chronically infected, T-cells were able to produce cytokines against the same peptide but no cytolysis could be detected. In conclusion, in the animal that was able to clear HCV infection not only cytokine production was observed but also cytolytic potential against specific MHC class I/peptide-combinations.
Предметные рубрики MeSH
Amino Acid SequenceAnimalsCD8-Positive T-LymphocytesCytokinesCytotoxicity, ImmunologicEpitopesGene ExpressionHepacivirusHepatitis CHistocompatibility Antigens Class IImmunity, CellularImmunity, HumoralImmunizationMolecular Sequence DataPan troglodytesViral Core ProteinsViral Hepatitis VaccinesViral Nonstructural ProteinsSerine EndopeptidasesNucleoside-TriphosphataseDEAD-box RNA HelicasesViral Proteases