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Altered pattern of cytokine production by peripheral blood CD2+ cells from B chronic lymphocytic leukemia patients
1Departamento de Medicina, Universidad de Alcalá de Henares, Madrid, Spain.
Insights
Cytokine production, including Interferon gamma (IFN-gamma) and Tumor Necrosis Factor (TNF-alpha), is elevated in CD2+ lymphocytes of B-cell chronic lymphocytic leukemia (B-CLL) patients compared to healthy individuals. These alterations may contribute to leukemic cell expansion.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of malignant lymphocytes.
- The role of T-cell activation and cytokine production in B-CLL pathogenesis is not fully understood.
Purpose of the Study:
- To investigate alterations in activation-induced cytokine production by CD2+ lymphocytes in B-CLL patients.
- To explore the relationship between cytokine levels and specific lymphocyte subsets in B-CLL.
Main Methods:
- Cytokine levels (IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-4) were measured using ELISA in PHA-stimulated CD2+ lymphocytes from B-CLL patients and healthy controls.
- Statistical correlations were analyzed between cytokine levels and lymphocyte subset percentages (CD3+CD45RO+, CD3-CD56+).
Main Results:
- B-CLL patients showed significantly higher production of IFN-gamma and TNF-alpha compared to healthy controls.
- IFN-gamma and TNF-alpha levels correlated with specific lymphocyte subsets in B-CLL patients.
- Non-smouldering B-CLL patients exhibited higher IFN-gamma and IL-4 production than smouldering B-CLL patients.
Conclusions:
- Functional alterations in CD2+ lymphocyte cytokine production are present in B-CLL.
- These cytokine dysregulations may play a role in the expansion of leukemic cells in B-CLL.
- Differential cytokine profiles exist between non-smouldering and smouldering B-CLL subtypes.
Abstract:
To determine if activation-induced cytokine production is altered in CD2+ lymphocytes from B-CLL patients, cytokine levels were determined by ELISA in supernatants of PHA-stimulated cultures of CD2+ cells from 33 B-CLL patients and 22 healthy controls. The production of Interferon gamma (IFN-gamma) and Tumor Necrosis Factor (TNF-alpha) by mitogen-activated CD2+ lymphocytes from B-CLL patients was higher than that found in healthy controls, while no differences were found in TNF-beta production. IFN-gamma and TNF-alpha levels determined at 72 h in PHA-stimulated CD2+ cell cultures from B-CLL patients statistically correlated with the percentages of CD3+CD45RO+ and CD3-CD56+ lymphocytes, respectively. Although there were differences in the production kinetics of interleukins (ILs) 2 and 4 between B-CLL patients and the healthy controls, no differences were found at the time when the levels of both interleukins peak. The production of both IFN-gamma and IL-4 by PHA-stimulated CD2+ lymphocytes from non-smouldering B-CLL patients was significantly higher than that from smouldering B-CLL patients while no significant differences were found in the production of IL-2, TNF-alpha, and TNF-beta between the two B-CLL patient groups. These data suggest that functional alterations in the production of cytokines by CD2+ cells from B-CLL patients could help to explain the expansion of leukemic cells in B-CLL patients.