title: Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population.
abstract: The proportion of human peripheral blood CD8+ T cells that are CD57+ CD28- is low at birth but increases with age and in individuals infected with human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV). These CD57+ CD28- CD8+ T cells contain large oligoclonal T-cell expansions whose antigen specificity is unknown. We identified clonal expansions of virus-specific memory cytotoxic T-lymphocyte precursors (CTLp) in both healthy carriers of HCMV and in asymptomatic HIV-infected subjects. In each subject, from the T-cell receptor (TCR) beta-chain hypervariable sequence of each immunodominant CTL clone, we designed complementary oligonucleotide probes to quantify the size and phenotypic segregation of individual virus-specific CTL clones in highly purified populations of peripheral blood CD8+ T cells. We found large clonal expansions of virus-specific CTL clonotypes in CD57+ CD28- CD8+ T cells. Using limiting dilution analysis, we found functional peptide-specific CTLp at high frequency in CD57+ CD28- cells. Thus, memory CTL specific for persistent viruses account for many oligoclonal expansions within CD57+ CD28- CD8+ T cells.
authors.affiliation: Department of Medicine, University of Cambridge Clinical School, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Weekes
authors.forename: M R
authors.initials: MR
authors.lastname: Wills
authors.forename: K
authors.initials: K
authors.lastname: Mynard
authors.forename: R
authors.initials: R
authors.lastname: Hicks
authors.forename: J G
authors.initials: JG
authors.lastname: Sissons
authors.forename: A J
authors.initials: AJ
authors.lastname: Carmichael
mesh_terms: D018106:CD28 Antigens / Q000276:immunology*; D018959:CD57 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens