title: Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia.
abstract: The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormality in CLL involves the clonal expansion of B cells. In this study we have undertaken a comprehensive analysis of the CD4+ and CD8+ T cell repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22). The TCR repertoire analysis was performed using a multiplex PCR assay for CDR3 length, an approach that allows for the detection of underlying oligoclonality in complex T cell populations. We established that oligoclonality was substantially more frequent in both the CD4+ and CD8+ T cell populations of CLL patients than in the age-matched controls (p < 0.001). Using three-color FACS analysis with a panel of TCRV segment-specific mAbs, we also established that oligoclonal expansions are predominantly found in the CD57+ subset of both the CD4+ and CD8+ T cell populations. The frequency of the CD57 marker on CD4+ T cells was increased in the setting of CLL (% CD57 = 14.8 +/- 13.0%) compared with that in normal controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4+CD57+ T cells was correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4+CD57+ T cells occurred in CLL patients who had progressed beyond Rai stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a role for clonal T cell populations in the pathogenesis of this disease.
authors.affiliation: Department of Medicine, North Shore University Hospital/New York University School of Medicine, Manhasset, NY 11030, USA.
authors.forename: D
authors.initials: D
authors.lastname: Serrano
authors.forename: J
authors.initials: J
authors.lastname: Monteiro
authors.forename: S L
authors.initials: SL
authors.lastname: Allen
authors.forename: J
authors.initials: J
authors.lastname: Kolitz
authors.forename: P
authors.initials: P
authors.lastname: Schulman
authors.forename: S M
authors.initials: SM
authors.lastname: Lichtman
authors.forename: A
authors.initials: A
authors.lastname: Buchbinder
authors.forename: V P
authors.initials: VP
authors.lastname: Vinciguerra
authors.forename: N
authors.initials: N
authors.lastname: Chiorazzi
authors.forename: P K
authors.initials: PK
authors.lastname: Gregersen
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018959:CD57 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*
chemical_list: D018959:CD57 Antigens; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta