Interleukin2

IL-2, a glycoprotein secreted mainly by activated T-cells, plays a critical role in the development of immune responses. In addition to inducing the proliferation and activation of T-lympho-cytes and cytotoxic cells, it may promote the production of other cytokines such as granulocyte/ macrophage colony-stimulating factor (GM-CSF), interferon-y (IFNy), and tumor necrosis factor-a (TNFa) (14,15).

The direct effect of IL-2 on CLL leukemic cells is exerted through the IL-2 receptors, whose presence has been demonstrated on the surface of CLL B-lymphocytes (16). IL-2 has a costimulatory effect on CLL cells, following a primary signal: CLL B-cells preactivated with anti-IgM and anti-CD40 have been shown to increase the incorporation of thymidine, a marker of proliferative activity (17,18). Proliferation was also observed in CLL cells upon culture with IL-2 alone (19).

The IL-2 pathway may also be involved in the survival of the leukemic clone through an indirect effect on the non-neoplastic T-cell compartment. Not only do CLL B-lymphocytes express IL-2 receptor on their surface, but they may also absorb exogenous IL-2 (20). In addition, CLL patients show increased levels of the soluble IL-2 receptor (21,22). Given the overwhelming number of CLL B-cells in the peripheral blood of CLL patients, both these circumstances may decrease the availability of IL-2 for the accessory T- and cytotoxic lymphocytes, thus impairing the efficacy of physiological immune responses (23). This may contribute to the numerous functional defects recorded within the T- and cytotoxic compartments of patients with CLL (24).

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