Uhrlaub Jennifer L, Smithey Megan J, Nikolich-Žugich Janko
Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724.
BIO5 Institute, University of Arizona College, Tucson, AZ 85721; and.
J Immunol. 2017 Jul 15;199(2):403-407. doi: 10.4049/jimmunol.1700625. Epub 2017 Jun 14.
The vertebrate immune system uses multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHC class I presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral Ags in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (∆12∆203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host antipoxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis. This also provides a proof of principle that suboptimal CD8 T cell in old organisms can be optimized by manipulating Ag presentation, with implications for vaccine design.
脊椎动物的免疫系统利用多种（有时是冗余的）机制来控制致病微生物，这些微生物一直在进化以逃避宿主防御。因此，牛痘病毒（CPXV）利用编码CPXV12和CPXV203的基因来阻止受感染细胞直接将病毒肽呈递给MHC I类分子。然而，在幼鼠中，CD8 T细胞通过病毒抗原的交叉呈递被有效地激活以对抗CPXV。老年小鼠在CD8 T细胞激活和交叉呈递方面都积累了缺陷。利用CPXV的双缺失突变体（∆12∆203），我们发现直接激活老年小鼠的CD8 T细胞能产生更强的回忆反应，证实了这一机制对宿主抗痘病毒反应的关键作用，并加深了我们对病毒对直接呈递的操纵如何影响发病机制的基本理解。这也提供了一个原理证明，即通过操纵抗原呈递可以优化老年生物体中次优的CD8 T细胞，这对疫苗设计具有启示意义。
