Autocrine and/or paracrine growth of adult T-cell leukaemia tumour cells by interleukin 15.

ABSTRACT

We previously demonstrated that interleukin 2 (IL-2) autocrine/paracrine growth in adult T-cell leukaemia (ATL) cells was closely correlated with clinical aggressiveness. In the present study, we compared the significance of IL-15 and IL-2 in growth of ATL cells and clinical aggressiveness. Thirty-seven patients with ATL were examined 19 acute and 18 chronic. Autonomous growth and IL-2- or IL-15-responsive growth activities of ATL cells were measured by [3H]-thymidine incorporation after 24 h cultures in vitro. All of the autonomous, IL-15- and IL-2-responsive growth activities of acute-type cells were higher than those of chronic type (P = 0.04, P = 0.03 and P = 0.02 respectively). IL-15- and IL-2-responsive growth activities were highly correlated (P = 0.0001, R2 = 0.837). Enzyme-linked immunosorbent assay (ELISA) showed detectable serum levels of IL-15 and IL-2 in 18 out of 19 and 14 out of 17 patients respectively. Reverse transcription polymerase chain reaction (RT-PCR) revealed IL-15 and IL-2 mRNA expression in 8 out of 11 patients' cells. Anti-IL-2 antibody partially inhibited autonomous growth of ATL cells; anti-IL-15 antibody was less effective. In situ immunochemistry detected IL-15 in cells of three patients and was consistent with the results of RT-PCR. These results suggest that ATL cells grow in an IL-15 autocrine/paracrine manner and that this growth is related to disease aggressiveness in a manner similar to IL-2.