Interleukin 4 content in chronic lymphocytic leukaemia (CLL) B cells and blood CD8+T cells from B-CLL patients: impact on clonal B-cell apoptosis

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Abstract
B‐chronic lymphocytic leukaemia (CLL) clonal B cells are characterized by resistance to apoptosis. We evaluated clonal B cells and blood T cells for interleukin 4 (IL‐4) content as IL‐4 is able to increase CLL cell resistance to apoptosis. The content of IL‐4 in CD8+ T cells of CLL patients (n = 9) ranged from 37% to 63% of the total CD8+ T cells (mean level of 49% ± 3·4) compared with a range of 5–10% for control CD8+ T cells. Clonal B cells positive for cytoplasmic IL‐4 ranged from 1% to 97% (mean value 57·8 ± 6·9%). CD8+ T cells and clonal B cells secreted detectable levels of IL‐4, but only clonal CLL B cells (n = 4) secreted IL−4 in association with increasing cell numbers. Fludarabine (F‐ara‐AMP, 0·1–100 μmol/ml) was able to downregulate the IL‐4 content of CD8+ T cells, but not clonal B‐cell IL‐4. Culture supernatant from CLL CD8+ T cells decreased the spontaneous apoptotic rate of clonal B cells that was reversed with anti‐IL‐4 and soluble IL‐4 receptor. These findings show that IL‐4 is present in the microenvironment of B‐CLL. In addition, use of agents that can interfere with IL‐4 presentation to clonal B cells can be effective in increasing clonal B‐cell apoptosis.

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