Generation of leukemia-specific T-helper type 1 cells applicable to human leukemia cell-therapy.
Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-gamma (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions were the most suitable for inducing leukemic DC expressing high levels of HLA and costimulatory molecules. Addition of IL-2 after 2 days of culture induced a preferential growth of minor T cell populations interacting with leukemic DC. In particular, IFN-gamma-producing CD4+ Th1 cells were efficiently expanded in type 1 culture conditions but nor in neutral or type 2-conditions. However, CD4+ T cells expanded in neutral conditions showed Th1-like functions if they were pulsed with IFN-gamma for 2 days before harvest. Such Th1 cells produced IFN-gamma and exhibited cytotoxicity in response to autologous leukemia cells. We further demonstrated that IFN-gamma production of leukemia-specific Th1 cells was blocked by anti-HLA-DR mAb. Thus, we established a novel culture system for inducing leukemia-specific Th1 cells.
Fujimura
Taku
T
Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Chamoto
Kenji
K
Tsuji
Takemasa
T
Sato
Takeshi
T
Yokouchi
Hiroshi
H
Aiba
Setsuya
S
Tagami
Hachiro
H
Tanaka
Junji
J
Imamura
Masahiro
M
Togashi
Yuji
Y
Koda
Toshiaki
T
Nishimura
Takashi
T
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D016313:Genes, abl; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma