title: Viral infections induce abundant numbers of senescent CD8 T cells.
abstract: 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.
authors.affiliation: Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Voehringer
authors.forename: C
authors.initials: C
authors.lastname: Blaser
authors.forename: P
authors.initials: P
authors.lastname: Brawand
authors.forename: D H
authors.initials: DH
authors.lastname: Raulet
authors.forename: T
authors.initials: T
authors.lastname: Hanke
authors.forename: H
authors.initials: H
authors.lastname: Pircher
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002455:Cell Division; D016922:Cellular Senescence; D037181:Lectins, C-Type; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011971:Receptors, Immunologic / Q000032:analysis; D014616:Vaccinia virus; D014721:Vesicular stomatitis Indiana virus; D014777:Virus Diseases / Q000276:immunology*
chemical_list: C423004:CLEC4A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic