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 gamm a chains, but IL-15R has a specific or chain distinct from that of IL- 2R alpha, which is indispensable for the high affinity binding of IL-1 5. 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 sti mulation with IL-2, and were maintained without IL-2. The responses to IL-15 were inhibited by the antibodies against IL-2R beta or gamma ch ains but was not by the IL-2R alpha chain antibody. [I-125]-IL-15 exhi bited a single high-affinity binding with an apparent kd of 0.17 nmol/ L. Reverse transcription-coupled polymerase chain reaction (RT-PCR) sh owed 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 line s did not secrete IL-15, and the culture supernatants of fresh ATL cel ls and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also res ponded to IL-15. These results suggest that ATL cells have the complet e form of IL-15R and respond to IL-15. Such an IL-15-dependent cell pr oliferation mechanism might be used in the development of AIL and for the invasion and proliferation of ATL cells in the visceral organs. (C ) 1998 by The American Society of Hematology.