Expression of functional interleukin‐21 receptor on adult T‐cell leukaemia cells

Summary Adult T‐cell leukaemia (ATL) is caused by human T‐cell leukaemia virus type I (HTLV‐I). It has been suggested that cytokines play a role in the development and in the neoplastic cell growth of ATL. However, the precise mechanism involved in this process still remains unclear. Interleukin‐21 (IL‐21) and its receptor (IL‐21R) have been recently described. In this study, we examined the expression of IL‐21R and the effect of IL‐21 on ATL cells. Real‐time reverse transcription polymerase chain reaction showed that HTLV‐I‐infected cell lines and primary ATL cells expressed IL‐21R mRNA. Cell surface expression of IL‐21R on these cells was confirmed by flow cytometric analysis using a newly developed monoclonal antibody against human IL‐21R. In contrast to the expression of IL‐21R, IL‐21 mRNA was scarcely detectable in these cells. Notably, IL‐21 induced the proliferation of ATL‐43T and ED‐40515(+) cells, both of which were derived from leukaemic cell clones of ATL. Concerning the intracellular signalling pathways, IL‐21 activated the phosphorylation of the signal transducers and activators of transcription (STAT)3 and STAT5. Taken together, these findings provide the first evidence that ATL cells express functional IL‐21R, suggesting that it may contribute to the pathophysiology of ATL. In addition, the IL‐21/IL‐21R system may represent a new target for the treatment of ATL.