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-gamma) is indicated to prevent malignant cells from entering apoptosis. The aim of the study was to determine IFN-gamma 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-gamma+ and CD3+/CD8+/IFN-gamma+ in patients than in controls (P < 0.001 in both cases). Moreover the percentage of CD3+/CD8+/IFN-gamma+ 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-gamma+ 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-gamma in B-CLL patients. The subset of CD3+/CD8+ cells expressing IFN-gamma 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.

Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases

“…Here, we could show that the amounts of TNF-␣ and IFN-␥ expressed by activated T cells from CLL in spontaneous regression are lower than those measured in progressive CLL, being similar to the levels found in patients with stable CLL or in healthy persons. This is in line with what was reported in the literature, [28][29][30][31] leading to the hypothesis that an increase in cytokine synthesis might be, among other factors, responsible for malignant cell accumulation in the BM microenvironment and for disease progression, preventing CLL cells from entering apoptosis.…”

Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia

“…Interactions of T cells with clinical course in B-CLL is not an unexpected finding, since alterations within the T-cell compartment that contribute to progressive disease have already been reported previously. Among these changes, aberrant expression of chemokines, 14 cytokines, 35,36 and costimulatory and adhesion molecules have been described, and a major part of these changes seems to be directly triggered by the tumor clone itself. 37 Besides changes within the conventional In contrast, the presence of at least 50% CD38 ϩ T cells predicted for significantly shorter treatment-free survival in male but not in female patients.…”

T Cell Leukemia-1 Modulates TCR Signal Strength and IFN-γ Levels through Phosphatidylinositol 3-Kinase and Protein Kinase C Pathway Activation

“…In this context, our results show that primed, TCL1 ϩ/Ϫ CD4 ϩ Th1 T cells have increased IFN-␥, which could provide apoptosis protection. In patients with high levels of TCL1 expression, such as those with B chronic lymphocytic leukemia or T-PLL, protection from apoptosis could be enhanced by heightened IFN-␥, which combined with slow growth also makes such tumors less sensitive to therapy (57,58).…”