The generation of leukemic dendritic cells from acute myeloid leukemia cells is potentiated by the addition of CD40L at the terminal maturation stage.
Leukemic dendritic cells (DCs) that are derived from acute myeloid leukemia (AML) cells display low-level expression of several key molecules. We investigated the optimal combination of cytokines needed to generate potent leukemic DCs from AML cells in vitro. AML cells were cultured in the presence of the following combinations of cytokines: Group A, granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha); Group B, GM-CSF + IL-4 + CD40L; and Group C, CD40L addition at the terminal maturation point of cells that were grown as for Group A. The AML cells showed clear upregulation of CD80, CD83, CD86, CD40, and HLA-DR expression under all culture conditions, without significant differences between these groups. However, the addition of CD40L (as in Group C) showed a slight upregulation in the expression of CD83 and CD86 on leukemic DCs. The leukemic DCs in Groups A and B had higher allogeneic T-cell stimulatory capacities than untreated AML cells, and the addition of CD40L (Group C) enhanced this effect. The function of the cytotoxicity-stimulating autologous T cells was also augmented by the addition of CD40L (Group C). These results suggest that AML cells may be used to generate leukemic DCs using various cytokine combinations, and that the most potent, mature leukemic DCs are generated by the addition of CD40L to terminal-stage AML cultures that are grown in the presence of conventional cytokine combinations.
Lee
Je-Jung
JJ
Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea. drjejung@chonnam.ac.kr
Choi
Bo-Hwa
BH
Nam
Jong-Hee
JH
Park
Myong-Suk
MS
Song
Won-Hyun
WH
Yang
Deok-Hwan
DH
Kim
Yeo-Kyeoung
YK
Cho
Sang-Hee
SH
Chung
Ik-Joo
IJ
Park
Kyeong-Soo
KS
Lee
Ii-Kwon
IK
Kim
Hyeoung-Joon
HJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D023201:CD40 Ligand / Q000494:pharmacology*; D003713:Dendritic Cells / Q000502:physiology*; D004705:Endocytosis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged
D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor