Heterogeneity of effector phenotype for acute phase and memory influenza A virus-specific CTL

J Immunol. 2007 Jul 1;179(1):64-70. doi: 10.4049/jimmunol.179.1.64.

Abstract

Ag-specific, CD8+ CTLs clear influenza A viruses from the lung via granzyme (Gzm) and perforin-dependent mechanisms. Ex vivo analysis of perforin-Gzm mRNA profiles demonstrated substantial heterogeneity in patterns of effector mRNA transcription of CD8+ D(b)NP(366)- or D(b)PA(224)-specific CTL. The only difference between the two epitope-specific sets was apparent very early after infection with similar molecular profiles seen in peak primary and secondary responses and in long-term memory. Surprisingly, memory T cells also expressed a diverse pattern of effector mRNA profile with an emphasis on GzmB and, surprisingly, GzmK. This analysis thus defines how naive, effector, and memory T cells differ in cytotoxic potential and provides novel insight into the molecular signatures of effector molecules observed at various stages after infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • H-2 Antigens / biosynthesis
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Immunologic Memory*
  • Immunophenotyping*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins
  • Nucleoproteins / biosynthesis
  • Nucleoproteins / immunology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / metabolism
  • Orthomyxoviridae Infections / pathology
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / immunology
  • RNA-Dependent RNA Polymerase / biosynthesis
  • RNA-Dependent RNA Polymerase / immunology
  • T-Lymphocytes, Cytotoxic / enzymology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology*
  • Viral Core Proteins / biosynthesis
  • Viral Core Proteins / immunology
  • Viral Proteins / biosynthesis
  • Viral Proteins / immunology

Substances

  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • Nucleoproteins
  • PA protein, influenza viruses
  • RNA-Binding Proteins
  • Viral Core Proteins
  • Viral Proteins
  • RNA-Dependent RNA Polymerase