Respiratory mucosal immunization with adenovirus gene transfer vector induces helper CD4 T cell‐independent protective immunity Journal Articles uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • AbstractBackgroundVirus‐vectored vaccine is a powerful activator of CD8 T cell‐mediated immunity and is especially amenable to respiratory mucosal immunization, offering hopes for use in humans with diminished helper CD4 T cell function. However, whether virus‐mediated mucosal immunization can produce immune protective CD8 T cells without the CD4 T cell help remains to be investigated.MethodsWe used a replication‐deficient adenovirus vector expressing an Mycobacterium tuberculosis antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell activation and protection in mice depleted of CD4 T cells.ResultsIntranasal vaccination of CD4 T cell‐depleted mice led to suboptimal generation of Ag‐specific tetramer+ or interferon (IFN)‐γ‐producing CD8 T cells in the lung and spleen but this was observed mainly at the early time after vaccination. Reduced CD8 T cell priming was also accompanied by decreased CD8 T cell responses (CTL). Nevertheless, the ratio of Ag‐specific CD8 T cells to IFN‐γ‐producing CD8 T cells in CD4 T cell‐depleted hosts remained comparable to that in CD4 T cell‐competent hosts. Furthermore, the ‘unhelped’ CD8 T cells also displayed a similar immune phenotype as the ‘helped’ counterparts. The animals with ‘unhelped’ CD8 T cells were as well‐protected from pulmonary M. tuberculosis challenge as those with ‘helped’ CD8 T cells in the absence of CD4 T cells.ConclusionsThe data obtained in the present study suggest that the fully immune protective CD8 T cells can still be generated by respiratory mucosal viral‐mediated immunization without CD4 T cells and that CD8 T cells, ‘helped’ or ‘unhelped’, can confer significant protection against pulmonary tuberculosis independent of CD4 T cells. Copyright © 2010 John Wiley & Sons, Ltd.

authors

  • Mu, Jingyu
  • Jeyanathan, Mangalakumari
  • Shaler, Christopher R
  • Horvath, Carly
  • Damjanovic, Daniela
  • Zganiacz, Anna
  • Kugathasan, Kapilan
  • McCormick, Sarah
  • Xing, Zhou

publication date

  • August 2010