Intracellular IFN-γ expression by CD3+/CD8+ cell subset in B-CLL patients correlates with stage of the disease

Abstract

Changes in the cytokine network may be responsible for malignant cell accumulation in B-cell chronic lymphocytic leukaemia (B-CLL). Among different cytokines of question interferon gamma (IFN-γ) is indicated to prevent malignant cells from entering apoptosis. The aim of the study was to determine IFN-γ production capacity of T-cell subsets and B lymphocytes in B-CLL patients in comparison with healthy individuals and during disease progression. Forty patients with newly diagnosed, untreated B-CLL and 20 healthy individuals were studied. The two- and three-colour flow cytometry techniques were used to detect intracellular cytokine expression. We detected statistically significantly higher percentage of both CD3+/CD4+/IFN-γ+ and CD3+/CD8+/IFN-γ+ in patients than in controls (P < 0.001 in both cases). Moreover the percentage of CD3+/CD8+/IFN-γ+ cells correlated with stage of the disease (R = 0.39, P = 0.01) and parameters of disease progression like lymphocyte count and total tumour mass score (R = 0.33, P = 0.03 and R = 0.31, P = 0.04, respectively). By contrast, the percentage of CD19+/IFN-γ+ cells in B-CLL group was lower than in controls (P < 0.01). These findings indicate that T-cell populations rather than malignant B cells are the source of IFN-γ in B-CLL patients. The subset of CD3+/CD8+ cells expressing IFN-γ seems to play a special role in the disease progression and more precise investigation should elucidate its role as a prognostic marker in B-CLL and a target for therapeutic strategies. © Blackwell Munksgaard 2004.