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Interleukin-15 (IL-15) Can Replace the IL-2 Signal in IL-2-Dependent Adult T-Cell Leukemia (ATL) Cell Lines: Expression of IL-15 Receptor alpha  on ATL Cells

Yasuaki Yamada, Kazuyuki Sugawara, Tomoko Hata, Kazuto Tsuruta, Ryozo Moriuchi, Takahiro Maeda, Sunao Atogami, Ken Murata, Kenshi Fujimoto, Tomoko Kohno, Kunihiro Tsukasaki, Masao Tomonaga, Yo-ichi Hirakata, and Shimeru Kamihira

From the Departments of Laboratory Medicine, Bacteriology, and Oncology, Nagasaki University School of Medicine; and the Department of Hematology, Atomic Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan.

Interleukin-15 receptor (IL-15R) and IL-2R have the same beta  and gamma  chains, but IL-15R has a specific alpha  chain distinct from that of IL-2Ralpha , which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R beta  or gamma  chains but was not by the IL-2R alpha  chain antibody. [125I]-IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription-coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R alpha . The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15-dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.

Blood, Vol. 91 No. 11 (June 1), 1998: pp. 4265-4272
© 1998 by The American Society of Hematology.


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