Distinctive patterns of naïve/memory subset distribution and cytokine expression in CD4 T lymphocytes in ZAP-70 B-chronic lymphocytic patients.

Background: ZAP-70 upregulation in B chronic lymphocytic leukemia (B-CLL) cells is a recognized marker of poor prognosis in these patients; the biological basis of this differential clinical outcome nonetheless remains unknown. ZAP-70 overexpression is considered a surrogate marker of a B-CLL cell subset. To test whether the differential biological characteristics of these patients also include the T helper population, we studied naïve, non-terminated memory (NTEM), terminated memory (TEM) and central memory (CM) cells, and cytokine expression by CD4 T lymphocytes from ZAP-70(+) and ZAP-70(-) B-CLL patients.

Methods: Expression of CD3, CD8, CD45RA, CD27, and CD28 antigens and intracytoplasmic cytokine production (IFNγ, IL-2, IL-4, IL-10, and TNFα) were assessed simultaneously by nine-color flow-cytometry in peripheral blood lymphocytes from B-CLL patients. B cell ZAP-70 expression in B-CLL cells was also analyzed by flow cytometry.

Results: Compared to ZAP-70(-) B-CLL patients, ZAP-70(+) B-CLL patients showed 1) significant reduction in the naïve T helper subset and expansion of NTEM and TEM subsets, 2) a decrease in the percentage of activated CD4 T lymphocytes expressing IFNγ, TNFα, and IL-2, and 3) an increase in the percentage of CD4 T lymphocytes expressing IL-4 or IL-10.

Conclusions: In conclusion, in early stage B-CLL patients, ZAP-70 upregulation is associated with distinct patterns of activation/differentiation stage subset distribution and of cytokine expression in CD4 T lymphocytes.