Expression of functional interleukin-21 receptor on adult T-cell leukaemia cells.
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.
Ueda
Maki
M
Department of Haematology and Oncology, Graduate School of Medicine, Kyoto University, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, Japan.
Imada
Kazunori
K
Imura
Akihiro
A
Koga
Hikari
H
Hishizawa
Masakatsu
M
Uchiyama
Takashi
T
D000328:Adult; D015153:Blotting, Western / Q000379:methods; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D015368:Human T-lymphotropic virus 1; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008894:Milk Proteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis*; D018123:Receptors, Interleukin / Q000235:genetics*; D053655:Receptors, Interleukin-21; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D008894:Milk Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators