Viral immune evasion due to persistence of activated T cells without effector function

Academic Article

Abstract

  • We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus- specific CD8 T cells expressed activation markers (CD69(hi), CD44(hi), CD62L(lo)) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8-CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.
  • Digital Object Identifier (doi)

    Author List

  • Zajac AJ; Blattman JN; Murali-Krishna K; Sourdive DJD; Suresh M; Altman JD; Ahmed R
  • Start Page

  • 2205
  • End Page

  • 2213
  • Volume

  • 188
  • Issue

  • 12