Quantitative and qualitative features of heterologous virus-vector-induced antigen-specific CD8⁺ T cells against Trypanosoma cruzi infection

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• 作者：Eiji Takayama ; Takeshi Ono ; Elena Carnero ; Saori Umemoto ; Yoko Yamaguchi ; Atsuhiro Kanayama ; Takemi Oguma ; Yasuhiro Takashima ; Takushi Tadakuma ; Adolfo Garcí ; a-Sastre ; Yasushi Miyahira
• 关键词：CD8⁺ T cells ; Trypanosoma cruzi ; Recombinant adenovirus ; Recombinant influenza virus ; Recombinant vaccinia virus
• 刊名：International Journal for Parasitology
• 出版年：2010
• 出版时间：November 2010
• 年：2010
• 卷：40
• 期：13
• 页码：1549-1561
• 全文大小：1119 K

文摘

We studied some aspects of the quantitative and qualitative features of heterologous recombinant (re) virus-vector-induced, antigen-specific CD8⁺ T cells against Trypanosoma cruzi. We used three different, highly attenuated re-viruses, i.e., influenza virus, adenovirus and vaccinia virus, which all expressed a single, T. cruzi antigen-derived CD8⁺ T-cell epitope. The use of two out of three vectors or the triple virus-vector vaccination regimen not only confirmed that the re-vaccinia virus, which was placed last in order for sequential immunisation, was an effective booster for the CD8⁺ T-cell immunity in terms of the number of antigen-specific CD8⁺ T cells, but also demonstrated that (i) the majority of cells exhibit the effector memory (T_EM) phenotype, (ii) robustly secrete IFN-γ, (iii) express higher intensity of the CD122 molecule and (iv) present protective activity against T. cruzi infection. In contrast, placing the re-influenza virus last in sequential immunisation had a detrimental effect on the quantitative and qualitative features of CD8⁺ T cells. The triple virus-vector vaccination was more effective at inducing a stronger CD8⁺ T-cell immunity than using two re-viruses. The different quantitative and qualitative features of CD8⁺ T cells induced by different immunisation regimens support the notion that the refinement of the best choice of multiple virus-vector combinations is indispensable for the induction of a maximum number of CD8⁺ T cells of high quality.