Autocrine and/or paracrine growth of adult T-cell leukaemia tumour cells by interleukin 15.
We previously demonstrated that interleukin 2 (IL-2) autocrine/paracrine growth in adult T-cell leukaemia (ATL) cells was closely correlated with clinical aggressiveness. In the present study, we compared the significance of IL-15 and IL-2 in growth of ATL cells and clinical aggressiveness. Thirty-seven patients with ATL were examined: 19 acute and 18 chronic. Autonomous growth and IL-2- or IL-15-responsive growth activities of ATL cells were measured by [3H]-thymidine incorporation after 24 h cultures in vitro. All of the autonomous, IL-15- and IL-2-responsive growth activities of acute-type cells were higher than those of chronic type (P = 0.04, P = 0.03 and P = 0.02 respectively). IL-15- and IL-2-responsive growth activities were highly correlated (P = 0.0001, R2 = 0.837). Enzyme-linked immunosorbent assay (ELISA) showed detectable serum levels of IL-15 and IL-2 in 18 out of 19 and 14 out of 17 patients respectively. Reverse transcription polymerase chain reaction (RT-PCR) revealed IL-15 and IL-2 mRNA expression in 8 out of 11 patients' cells. Anti-IL-2 antibody partially inhibited autonomous growth of ATL cells; anti-IL-15 antibody was less effective. In situ immunochemistry detected IL-15 in cells of three patients and was consistent with the results of RT-PCR. These results suggest that ATL cells grow in an IL-15 autocrine/paracrine manner and that this growth is related to disease aggressiveness in a manner similar to IL-2.
Kukita
Toshimasa
T
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Arima
Naomichi
N
Matsushita
Kakushi
K
Arimura
Kosei
K
Ohtsubo
Hideo
H
Sakaki
Yoshimune
Y
Fujiwara
Hiroshi
H
Ozaki
Atsuo
A
Matsumoto
Tadashi
T
Tei
Chuwa
C
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015461:Leukemia, Prolymphocytic, T-Cell / Q000473:pathology; D015458:Leukemia, T-Cell / Q000473:pathology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger