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.
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.
Yamada
Y
Y
Department of Laboratory Medicine, Nagasaki University School of Medicine, Medicine, Nagasaki, Japan.
Sugawara
K
K
Hata
T
T
Tsuruta
K
K
Moriuchi
R
R
Maeda
T
T
Atogami
S
S
Murata
K
K
Fujimoto
K
K
Kohno
T
T
Tsukasaki
K
K
Tomonaga
M
M
Hirakata
Y
Y
Kamihira
S
S
D000328:Adult; D000906:Antibodies / Q000378:metabolism; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000906:Antibodies; C508024:IL15RA protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2