Viral infections induce abundant numbers of senescent CD8 T cells

J Immunol. 2001 Nov 1;167(9):4838-43. doi: 10.4049/jimmunol.167.9.4838.


Viral infections are often accompanied by extensive proliferation of reactive CD8 T cells. After a defined number of divisions, normal somatic cells enter a nonreplicative stage termed senescence. In the present study we have identified the inhibitory killer cell lectin-like receptor G1 (KLRG1) as a unique marker for replicative senescence of murine CD8 T cells. KLRG1 expression was induced in a substantial portion (30-60%) of CD8 T cells in C57BL/6 mice infected with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus, or vaccinia virus. Similarly, KLRG1 was found on a large fraction of LCMV gp33 peptide-specific TCR-transgenic (tg) effector and memory cells activated in vivo using an adoptive transfer model. Transfer experiments with CFSE-labeled TCR-tg cells into LCMV-infected hosts further indicated that induction of KLRG1 expression required an extensive number of cell divisions. Most importantly, KLRG1(+) TCR-tg effector/memory cells could efficiently lyse target cells and secrete cytokines, but were severely impaired in their ability to proliferate after Ag stimulation. Thus, this study demonstrates that senescent CD8 T cells are induced in abundant numbers during viral infections in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Division
  • Cellular Senescence*
  • Lectins, C-Type*
  • Lymphocytic Choriomeningitis / immunology
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Receptors, Immunologic / analysis
  • Vaccinia virus
  • Vesicular stomatitis Indiana virus
  • Virus Diseases / immunology*


  • CLEC4A protein, human
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Receptors, Immunologic