title: Human virus-specific CD8+ CTL clones revert from CD45ROhigh to CD45RAhigh in vivo: CD45RAhighCD8+ T cells comprise both naive and memory cells.
abstract: It has been generally believed that human CD8+ memory cells are principally found within the CD45ROhigh population. There are high frequencies of CD8+ memory CTL specific for the human CMV tegument phosphoprotein pp65 in PBMC of long-term virus carriers; the large population of memory CTL specific for a given pp65 peptide contains individual CTL clones that have greatly expanded. In this study, we found high frequencies of pp65 peptide-specific memory CTL precursors in the CD45ROhighCD45RA- population, but also appreciable frequencies in the CD45RAhigh subpopulation. Because the majority of CD8+ T cells in PBMC are CD45RAhigh, more of the total pp65-specific memory CTL pool is within the CD45RAhigh than in the CD45ROhigh compartment. Using clonotypic oligonucleotide probes to quantify the size of individual pp65-specific CTL clones in vivo, we found the CD45RAhigh population contributed 6- to 10-fold more than the CD45ROhigh population to the total virus-specific clone size in CD8+ cells. During primary CMV infection, an individual virus-specific CTL clone was initially CD45ROhigh, but after resolution of infection this clone was detected in both the CD45ROhigh and the CD45RAhigh populations. We conclude that CD45RA+ human CD8+ T cells do not solely comprise naive cells, but contain a very significant proportion of memory cells, which can revert from the CD45ROhigh to CD45RAhigh phenotype in vivo.
authors.affiliation: Department of Medicine, University of Cambridge Clinical School, United Kingdom. mrw1004@mole.bio.cam.ac.uk
authors.forename: M R
authors.initials: MR
authors.lastname: Wills
authors.forename: A J
authors.initials: AJ
authors.lastname: Carmichael
authors.forename: M P
authors.initials: MP
authors.lastname: Weekes
authors.forename: K
authors.initials: K
authors.lastname: Mynard
authors.forename: G
authors.initials: G
authors.lastname: Okecha
authors.forename: R
authors.initials: R
authors.lastname: Hicks
authors.forename: J G
authors.initials: JG
authors.lastname: Sissons
mesh_terms: D002353:Carrier State / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D017493:Leukocyte Common Antigens