Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Gail D. Sckisel, Julia K. Tietze, Anthony E. Zamora, Hua Hui Hsiao, Stephen O. Priest, Danice E C Wilkins, Louis L. Lanier, Bruce R. Blazar, Nicole Baumgarth, William J. Murphy

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8+ T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8+ T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44highCD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbumin-specific (OT-I) CD8+ T cells, which are not specific to influenza. These non-specific CD8+ T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8+ T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8+ T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

Original languageEnglish (US)
Pages (from-to)79-91
Number of pages13
JournalClinical and Experimental Immunology
Issue number1
StatePublished - Jan 2014


  • Antigen non-specific
  • Bystander activation
  • Memory CD8
  • NKG2D
  • Tissue-resident


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