Interleukin-4 induces proliferation of adult T-cell leukemia cells.
To evaluate the effect of IL-4 on the growth of leukemic cells from adult T-cell leukemia (ATL) patients (ATL cells) and determine whether the IL-4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL-4 in vitro. Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL-2 and IL-4 in a dose-dependent manner. The proliferative response to IL-4 was higher than that obtained with IL-2 in 8 patients. The expression of the IL-2 receptor (IL-2R) alpha alpha-chain in leukemic cells from some patients was also enhanced by IL-4. The IL-4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL-4-induced proliferation of ATL cells nor IL-4-induced IL-2R expression on ATL cells was inhibited by anti-Tac or anti-IL-2 antibody and, therefore, these effects of IL-4 are considered independent of endogenous IL-2 activity. However, IL-2 and IL-4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme-linked immunosorbent assay. Interferon-gamma (IFN-gamma) partially inhibited IL-2 or IL-4-induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL-2 or IL-4 paracrine mechanism in lymphoid tissue in vivo and that IFN-gamma inhibits IL-2- or IL-4-induced proliferation of ATL cells.
Mori
N
N
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Yamashita
U
U
Tanaka
Y
Y
Nakata
K
K
Oda
S
S
Morimoto
I
I
Eto
S
S
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D015458:Leukemia, T-Cell / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma