title: CD8highCD57+ T lymphocytes in normal, healthy individuals are oligoclonal and respond to human cytomegalovirus.
abstract: CD8+CD57+ lymphocytes from normal peripheral blood are divided into T cells expressing high levels of CD8 and NK cells expressing low levels of surface CD8. Increased numbers of CD8highCD57+ T cells correlate with previous exposure to human cytomegalovirus (HCMV) infection, but no virus-specific function or function for CD8highCD57+ cells has been recorded. We have studied the TCR repertoire and responses of the CD8highCD57+ population induced by virus-infected fibroblasts in healthy individuals. Using three-color flow cytometry of PBL, we detected restricted TCRBV usage in the CD8highCD57+ subset of 11/15 subjects, compared with 1/15 in the CD8+, CD57- subset. The results of anchored PCR and sequencing also showed oligoclonality of TCR; 40-70% of CD8highCD57+ lymphocytes (10-20% of total CD8+ T cells) were derived from single clones. Such expansions were stable with time and detected in one subject over a 2-yr period. Functionally, CD8highCD57+ lymphocytes proliferated strongly to HCMV-, but not HSV-, VZV-, or influenza-infected fibroblasts in an MHC-unrestricted manner in vitro, including preferential augmentation of particular in vivo oligoclonally expanded subpopulations. HCMV-specific MHC-restricted CTL were detected, but limiting dilution analysis showed that these were a minority (< 10%) and not the oligoclonal subsets. In contrast, depletion of oligoclonally expanded CD8highCD57+ subpopulations, resulted in the increase of HCMV-specific CTL, suggesting functional heterogeneity in these cells.
authors.affiliation: Department of Medicine, University of Wales College of Medicine, Health Hospital, Cardiff, United Kingdom.
authors.forename: E C
authors.initials: EC
authors.lastname: Wang
authors.forename: P A
authors.initials: PA
authors.lastname: Moss
authors.forename: P
authors.initials: P
authors.lastname: Frodsham
authors.forename: P J
authors.initials: PJ
authors.lastname: Lehner
authors.forename: J I
authors.initials: JI
authors.lastname: Bell
authors.forename: L K
authors.initials: LK
authors.lastname: Borysiewicz
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018959:CD57 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
chemical_list: D018959:CD57 Antigens; D011948:Receptors, Antigen, T-Cell