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.
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.
Melenhorst
J Joseph
JJ
Stem Cell Allotransplantation Section, NHLBI, NIH, Bethesda, MD 20892, USA. melenhoj@nih.gov
Eniafe
Rhoda
R
Follmann
Dean
D
Molldrem
Jeffrey
J
Kirby
Martha
M
El Ouriaghli
Frank
F
Barrett
A John
AJ
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
D018959:CD57 Antigens; D004273:DNA, Neoplasm; D016693:Receptors, Antigen, T-Cell, alpha-beta