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Keywords:

  • B-CLL;
  • B cells;
  • T cells;
  • IL-4;
  • apoptosis

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.