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
Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
PLoS One. 2014 Apr 16;9(4):e95103. doi: 10.1371/journal.pone.0095103. eCollection 2014.
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.
针对慢性丙型肝炎病毒（HCV）感染的有效疫苗保护的单一关联因素尚未明确。在本研究中，我们分析了四只黑猩猩的T细胞反应，这些黑猩猩用核心-E1-E2-NS3免疫，随后感染HCV1b。在一只动物中观察到病毒清除，而其他三只则发生慢性感染。在清除感染的动物中，就产生细胞因子的细胞的频率和多功能性而言，NS3特异性CD8 T细胞反应更为有效。这只动物独特之处在于存在具有杀伤能力的CD8 T细胞，其对NS3 1258-1272具有特异性，由黑猩猩MHC I类分子Patr-A*03∶01呈递，并且对该表位具有高亲和力识别。在发生慢性感染的动物中，T细胞能够产生针对相同肽的细胞因子，但未检测到细胞溶解作用。总之，在能够清除HCV感染的动物中，不仅观察到细胞因子产生，而且还观察到针对特定MHC I类/肽组合的细胞溶解潜力。
