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

Allan J. Zajac, Joseph N. Blattman, Kaja Murali-Krishna, David J.D. Sourdive, M. Suresh, John D. Altman, Rafi Ahmed

Research output: Contribution to journalArticle

1324 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2205-2213
Number of pages9
JournalJournal of Experimental Medicine
Volume188
Issue number12
DOIs
StatePublished - Dec 1 1998
Externally publishedYes

Keywords

  • CD4 T cells
  • Chronic infections
  • Cytotoxic T cells
  • Major histocompatibility complex tetramers
  • Unresponsiveness

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Suresh, M., Altman, J. D., & Ahmed, R. (1998). Viral immune evasion due to persistence of activated T cells without effector function. Journal of Experimental Medicine, 188(12), 2205-2213. https://doi.org/10.1084/jem.188.12.2205