Department of Global Infectious Diseases and Tropical Medicine, National Defense Medical College, Tokorozawa City, Saitama, Japan.
Int J Parasitol. 2010 Nov;40(13):1549-61. doi: 10.1016/j.ijpara.2010.05.011. Epub 2010 Jul 8.
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.
我们研究了异源重组（re）病毒载体诱导的针对克氏锥虫的抗原特异性 CD8(+) T 细胞的定量和定性特征的某些方面。我们使用了三种不同的、高度减毒的 re 病毒，即流感病毒、腺病毒和痘苗病毒，它们都表达了一个单一的、源自克氏锥虫抗原的 CD8(+) T 细胞表位。使用三种载体中的两种或三重病毒载体疫苗接种方案不仅证实了顺序免疫中最后放置的 re 痘苗病毒在数量上是针对 CD8(+) T 细胞免疫的有效增强剂（+) T 细胞，而且还表明 (i) 大多数细胞表现出效应记忆 (T(EM)) 表型，(ii) 强烈分泌 IFN-γ，(iii) 表达更高强度的 CD122 分子，以及 (iv) 对克氏锥虫感染具有保护活性。相比之下，将 re 流感病毒最后放置在顺序免疫中会对 CD8(+) T 细胞的定量和定性特征产生不利影响。三重病毒载体疫苗接种比使用两种 re 病毒更有效地诱导更强的 CD8(+) T 细胞免疫。不同免疫方案诱导的 CD8(+) T 细胞的不同定量和定性特征支持这样一种观点，即对最佳多病毒载体组合的选择进行细化对于诱导最大数量的高质量 CD8(+) T 细胞是必不可少的。
