title: Memory inflation: continuous accumulation of antiviral CD8+ T cells over time.
abstract: CD8+ T lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. This is particularly true in the case of persistent herpesviruses such as human CMV, which are typified by large virus-specific CD8+ T cell populations during viral latency. To understand the origin of these populations and the factors shaping them over time, we investigated the CD8+ T cell response after murine CMV (MCMV) infection. The kinetics of the acute response were characterized by rapid expansion of activated T cells, followed by a contraction phase. Thereafter, we observed a striking pattern, where MCMV-specific memory CD8+ T cells steadily accumulated over time, with 20% of all CD8+ T cells at 1 year specific for one MCMV epitope. Accumulation of MCMV-specific CD8+ T lymphocytes was seen in all organs tested and was associated with continuous activation of specific CD8+ T lymphocytes, primarily within lymph nodes. The pattern of accumulation was observed in only two of five epitopes tested, and was accompanied by a gradual restriction in usage of the variable region of the TCR beta-chain over time. This novel pattern of a virus-specific CD8+ T cell response suggests that continuous or repetitive exposure to Ag can slowly mold memory T cell populations over time. This may be relevant for understanding the evolution of the large human CMV-specific CD8+ T cell populations seen in humans.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK. urs.jarrer@dim.usz.ch
authors.forename: Urs
authors.initials: U
authors.lastname: Karrer
authors.forename: Sophie
authors.initials: S
authors.lastname: Sierro
authors.forename: Markus
authors.initials: M
authors.lastname: Wagner
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D017874:Immediate-Early Proteins / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D009928:Organ Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D017874:Immediate-Early Proteins; C052612:cytomegalovirus immediate early phosphoprotein pp89