title: T-cell large granular lymphocyte leukemia is characterized by massive TCRBV-restricted clonal CD8 expansion and a generalized overexpression of the effector cell marker CD57.
abstract: BACKGROUND
  Large granular lymphocyte leukemia (LGL) is a clonal lymphoproliferative disease of CD8+ T cells expressing the CD57 activation marker. It is, however, unknown whether the CD57+ population represents the LGL clone or not. We previously demonstrated that the clone can be found in both CD8+CD57+ and CD8+CD57- cells, indicating that the LGL clone also resides in the CD57- fraction.
  
  
  METHODS
  Here, we quantified the extent of the clonal CD8 expansion in LGL using T-cell receptor Vbeta (TCRBV)-specific monoclonal antibodies, and determined whether the CD4 population also contained skews. Furthermore, dominant TCRBV populations were assessed for clonal status using T-cell receptor-gamma (TCRG) PCR on genomic DNA.
  
  
  RESULTS
  We show that the dominant TCRBV in LGL contains CD57+ and CD57- cells. Molecular analysis of CD8+CD57+ and CD8+CD57- subfractions of the dominant TCRBV by TCRG PCR demonstrates that indeed both fractions are clonal, and that the clone is absent from the dominant TCRBV-negative population. Furthermore, we show that CD57 overexpression is not restricted to the LGL clone, but a general phenomenon in CD8 cells of LGL patients.
  
  
  CONCLUSIONS
  We therefore conclude that the primary characteristic of LGL is a clonal expansion of CD8 cells, with a concomitant upregulation of CD57 on this clone and uninvolved cells.
authors.affiliation: Stem Cell Allotransplantation Section, NHLBI, NIH, Bethesda, MD 20892, USA. melenhoj@nih.gov
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Melenhorst
authors.forename: Rhoda
authors.initials: R
authors.lastname: Eniafe
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Molldrem
authors.forename: Martha
authors.initials: M
authors.lastname: Kirby
authors.forename: Frank
authors.initials: F
authors.lastname: El Ouriaghli
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D015458:Leukemia, T-Cell / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000737:chemistry
chemical_list: D018959:CD57 Antigens; D004273:DNA, Neoplasm; D016693:Receptors, Antigen, T-Cell, alpha-beta