In vivo dynamics of anti-viral CD8 T cell responses to different epitopes. An evaluation of bystander activation in primary and secondary responses to viral infection

Adv Exp Med Biol. 1998;452:123-42. doi: 10.1007/978-1-4615-5355-7_14.

Abstract

Viral infections induce extensive T cell proliferation in vivo. However, only a small fraction (1-5%) of the activated T cells have been shown to be virus specific leading to the prevailing notion that most of the T cell expansion represents cytokine-mediated by-stander activation and/or cross reactive stimulation of non specific cells. To re-examine this issue we quantitated antigen specific CD8 T cells during acute LCMV infection of mice using three sensitive techniques: (i) intracellular cytokine production, (ii) single cell ELISPOT and (iii) direct visualization of antigen specific CD8 T cells by staining with MHC class I tetramers + peptide. In contrast to previous estimates, we found that 50-70% of the activated CD8 T cells were LCMV specific. This represented > or = 10,000-fold increase (approximately 2 x 10(7) virus specific cells/spleen) in 8 days with the peak expansion occurring between day 3 and 5 during which period virus specific CD8 T cells had an estimated division time of approximately 8 hours. Following viral clearance, the number of antigen specific CD8 T cells dropped to 1 x 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, memory CD8 T cells rapidly proliferated and again comprised > 50% of the total CD8 T cells. In contrast, upon challenge with a heterologous virus such as vaccinia, there was no change in the number of LCMV specific memory CTL, despite a substantial increase in the number of activated CD8 T cells. Taken together, these results show that much of the CD8 T cell expansion seen during viral infection represents antigen specific cells.

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 / immunology*
  • Cytotoxicity, Immunologic
  • Epitopes / immunology*
  • Female
  • Lymphocyte Activation
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL

Substances

  • Antigens, Viral
  • Epitopes