Cytoplasmic Interleukin-4 (IL-4) and Surface IL-4 Receptor Expression in Patients With B-Cell Lymphocytic Leukemia

To the Editor:

B-cell chronic lymphocytic leukemia (B-CLL) is a malignancy characterized by the accumulation of long-lived CD5⁺cells1 in which cytokines might be involved in the proliferation and survival of malignant B cells.2-6 

In particular, interleukin-4 (IL-4) prevents B-CLL cell clones from entering spontaneous apoptosis by increasing the expression of bcl-2⁵ and protects B-CLL cells against anti-APO1–induced apoptosis.6 Only one report has analyzed the intracellular expression of IL-4 in T cells of patients with B-CLL.7 We examined the expression of IL-4 and IL-4 receptor (IL-4R) in unstimulated leukemic B cells and T cells from 10 patients with untreated stage A B-CLL and compared them with 10 normal controls using flow cytometric analyses.

We found that the proportion of CD19⁺ cells expressing cytoplasmic IL-4 was significantly higher in B-CLL patients than in controls (P < .002; Table1). The proportion of CD3⁺cells expressing cytoplasmic IL-4 was significantly higher in B-CLL patients than in controls (P < .02). Although the proportion of CD19⁺ cells expressing IL-4R was similar, the proportion of CD3⁺ cells expressing the IL-4R in B-CLL patients was significantly higher than in normal controls (P < .02). IL-4 could not be detected in the supernatant after the in vitro culture of the cells from both patients and controls. After stimulation with the mitogen PWM, six of the seven control samples and none of the patient cells had detectable supernatant IL-4 (P < .03; Table2).

The demonstration that T cells from B-CLL patients display a greater percentage of IL-4R expression from normal individuals is novel. It is unclear whether the T cells from B-CLL patients express both the IL-4R together with IL-4 or this aberrant expression occurs on different T-cell populations in these patients. It is intriguing that no increase in IL-4R expression could be found on malignant B-CLL cells despite the expression of cytoplasmic IL-4. It is possible that the IL-4 from the B-CLL B cells is released and taken up rapidly by the T cells, and this leads to the aberrant expression of the IL-4R. Alternatively, the interaction between the malignant B cells and T cells may occur in a microenvironment in which local concentrations of IL-4 may be high, but these are not reflected in the blood. The disproportionate relationship between IL-4 and its receptor in the normal T-cell compartment compared with the malignant B-cell compartment in B-CLL is presumably important in the pathogenesis of B-CLL and merits further investigation.