Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge

Immunity. 2010 Jul 23;33(1):96-105. doi: 10.1016/j.immuni.2010.06.016.


Memory CD8(+) T cells in the lung airways provide protection from secondary respiratory virus challenge by limiting early viral replication. Here, we demonstrate that although airway-resident memory CD8(+) T cells were poorly cytolytic, memory CD8(+) T cells recruited to the airways early during a recall response showed markedly enhanced cytolytic ability. This enhanced lytic activity did not require cognate antigen stimulation, but rather was dependent on STAT1 transcription factor signaling through the interferon-alpha receptor (Ifnar1), resulting in the antigen-independent expression of granzyme B protein in both murine and human virus-specific T cells. Signaling through Ifnar1 was required for the enhanced lytic activity and control of early viral replication by memory CD8(+) T cells in the lung airways. These findings demonstrate that innate inflammatory signals act directly on memory T cells, enabling them to rapidly destroy infected host cells once they enter infected tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Cytotoxicity, Immunologic
  • Granzymes / biosynthesis*
  • Granzymes / genetics
  • Humans
  • Immunization, Secondary
  • Immunologic Memory
  • Influenza A virus / pathogenicity
  • Influenza A virus / physiology*
  • Interferon Type I / immunology
  • Interferon Type I / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Radiation Chimera
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Respiratory Mucosa / pathology
  • Respirovirus Infections / immunology*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • Sendai virus / pathogenicity
  • Sendai virus / physiology*
  • Signal Transduction
  • Virus Replication


  • Antigens, Viral
  • Interferon Type I
  • STAT1 Transcription Factor
  • Receptor, Interferon alpha-beta
  • Granzymes