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

Introduction: 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. Materials and methods: Here, we quantified the extent of the clonal CD8 expansion in LGL using T-cell receptor Vβ (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-γ (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. Conclusion: 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.