title: Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.
abstract: The viruses HIV-1, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed studies of the differentiation phenotype of these cells, which can be separated into three distinct subsets based on expression of the costimulatory receptors CD28 and CD27. Whereas CD8+ T cells specific for HIV, EBV and HCV exhibit similar characteristics during primary infection, there are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections. These findings challenge the current definitions of memory and effector subsets in humans, and suggest that ascribing effector and memory functions to subsets with different differentiation phenotypes is no longer appropriate.
authors.affiliation: MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. vappay@gwmail.jr2.ox.ac.uk
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: P Rod
authors.initials: PR
authors.lastname: Dunbar
authors.forename: Margaret
authors.initials: M
authors.lastname: Callan
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Geraldine M A
authors.initials: GM
authors.lastname: Gillespie
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
authors.forename: Abigail
authors.initials: A
authors.lastname: King
authors.forename: Franziska
authors.initials: F
authors.lastname: Lechner
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Norbert
authors.initials: N
authors.lastname: Gruener
authors.forename: Gerd
authors.initials: G
authors.lastname: Pape
authors.forename: Anele
authors.initials: A
authors.lastname: Waters
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology; D003603:Cytotoxins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology
chemical_list: C515370:CCR7 protein, human; D018106:CD28 Antigens; D003603:Cytotoxins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens