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- Title
Large granular lymphocyte leukaemia is characterized by a clonal T-cell receptor rearrangement in both memory and effector CD8<sup>+</sup> lymphocyte populations.
- Authors
Melenhorst, J. Joseph; Sorbara, Lynn; Kirby, Martha; Hensel, Nancy F.; Barrett, A. John
- 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 γ (TCRγ) 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.
- Subjects
LYMPHOCYTIC leukemia; T cell receptors; LYMPHOCYTES; CD antigens
- Publication
British Journal of Haematology, 2001, Vol 112, Issue 1, p189
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2001.02509.x