Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection

Immunity. 1998 Feb;8(2):177-87. doi: 10.1016/s1074-7613(00)80470-7.


Viral infections induce extensive T cell proliferation in vivo, but the specificity of the majority of the responding T cells has not been defined. To address this issue we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells during acute LCMV infection of mice. Based on tetramer binding and two sensitive assays measuring interferon-gamma production at the single-cell level, we found that 50%-70% of the activated CD8 T cells were LCMV specific [2 x 10(7) virus-specific cells/spleen]. Following viral clearance, antigen-specific CD8 T cell numbers dropped to 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, there was rapid expansion of memory T cells, but after infection with the heterologous vaccinia virus there was no detectable change in the numbers of LCMV-specific memory CTL. Therefore, much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of our current thinking on the size of the antiviral response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Immunity, Active
  • Immunologic Memory
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation*
  • Lymphocyte Count / methods*
  • Lymphocytic Choriomeningitis / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peptide Fragments / immunology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Viral
  • Histocompatibility Antigens Class I
  • Peptide Fragments
  • Interferon-gamma