title: Large granular lymphocyte leukaemia is characterized by a clonal T-cell receptor rearrangement in both memory and effector CD8(+) lymphocyte populations.
abstract: Large granular lymphocyte (LGL) leukaemia is a disease with increased numbers of circulating granular lymphocytes and an increased percentage of clonally rearranged CD8(+)CD57(+) cells. To determine whether LGL cells are also found in other lymphocyte subsets, CD8(+) cells from 10 LGL patients were sorted into CD57(+) and CD57(-) fractions and analysed for clonality using a T-cell receptor gamma (TCR gamma) polymerase chain reaction (PCR). In nine patients, a clonal TCR rearrangement was identified in the CD8(+)CD57(+) cells, and in one patient, the TCR rearrangement was oligoclonal in the CD8(+)CD57(+) fraction. In eight out of nine of the clonally rearranged patients, the same band was also present in the CD8(+)CD57(-) fraction. To define the relationship between CD57(-) and CD57(+) LGL populations, CD8(+)CD57(-) and CD8(+)CD57(+) cells were sorted from five patients and cultured in the presence of anti-CD3 plus CD28 antibodies. The CD57(+) cells died of apoptosis before d 7, while the CD57(-) cells proliferated and differentiated into CD57(+) cells. Clonal analysis identified the same band in both cultured subpopulations and in the uncultured CD8(+) cells. Immunophenotypical analysis showed that CD8(+)CD57(-) cells expressed memory cell markers, while the CD8(+)CD57(+) cells exhibited effector characteristics. These results suggest that LGL disease originates in a CD57(-) memory T-cell compartment that continually generates CD57(+) (effector cell) progeny.
authors.affiliation: Bone Marrow transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. melenhoj@nih.gov
authors.forename: J J
authors.initials: JJ
authors.lastname: Melenhorst
authors.forename: L
authors.initials: L
authors.lastname: Sorbara
authors.forename: M
authors.initials: M
authors.lastname: Kirby
authors.forename: N F
authors.initials: NF
authors.lastname: Hensel
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D018959:CD57 Antigens; D002454:Cell Differentiation; D002478:Cells, Cultured; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018959:CD57 Antigens