IL-2-induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF-κB induction and IL-2 receptor α expression

The binding of interleukin-2 (IL-2) to its receptor on normal T cells induces nuclear expression of nuclear factor kappa B (NF-kappa B), activation of the IL-2 receptor (IL-2R) alpha chain gene, and cell proliferation. In the present study, the role of IL-2R signaling in the growth of CD8(+) T cell prolymphocytic leukemia (T-PLL) cells has been investigated. Flow cytometry revealed that primary leukemia cells from a patient with CD8(+) T-PLL expressed IL-2R alpha and beta chains, and the cells showed a proliferative response and an increase in IL-2R alpha expression on culture with exogeneous IL-2. Northern blot analysis failed to detect IL-2 mRNA, suggesting that IL-2 may act in a paracrine manner in vivo. Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF-kappa B binding activity in nuclear extracts of the leukemia cells, and Northern blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF-kappa B components c-Rel and KBF1 in these cells. IL-2 binding analysis demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on the leukemia cells, without an effect on the number of high-affinity IL-2Rs. These results show that IL-2 is capable of inducing the nuclear expression of NF-kappa B in primary CD8(+) T-PLL cells, and that this effect is mediated, at least in part, at a pretranslational level. (C) 1998 Elsevier Science Ltd. All rights reserved.