[Immune response of dendritic cells capturing antigens from apoptotic U937 cells induced by artesunate].
The objective of study was to investigate whether U937 cells-loaded dendritic cells (DCs) could induce anti-leukemic immune activity. The apoptosis of U937 cells was induced by artesunate (ART). DCs derived from peripheral blood mononuclear cells of health donors were loaded with apoptotic U937 cells, and induced to maturation in the presence of TNF-alpha. Matured DCs were cocultured with autologous T-lymphocytes, and combined with IL-2 in order to induce the leukemia-specific CTL. The phenotypes of DCs and T lymphocytes were tested by flow cytometry. The ability of DC capturing antigens was measured by Dextran-FITC endocytosis. The IL-12p70 level was assayed by ELISA kit. The proliferation of CTL and CTL activity were measured by MTT assay. The results showed that the apoptotic rate of the U937 cells was 51.2% when U937 cells were induced by 1 microg/ml ART for 48 hours in vitro. DCs had the most powerful ability of endocytosis in its immature phase. Apoptotic U937 cells could not induce the features of DC maturation, and apoptotic U937 cell-pulsed immature DCs could be matured with TNF-alpha. The IL-12p70 level secreded by apoptotic U937 cell-loaded mature DCs (mDC-(Apo)U937) was higher than that of non-loaded mDC. The proliferation of autologous T lymphocytes co-cultured with mDC-(Apo)U937 was significantly remarkable and the content of CD8(+) CTL was significantly higher in comparison with any other groups. CTL induced by mDC-(Apo)U937 had stronger killing effect on U937 cells than NB4 (p < 0.01). It is concluded that the mDC-(Apo)U937 can effectively generate T cell-mediated dendritic antileukemic responses in vitro.
Zheng
Zhi-Yin
ZY
Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310006, China.
Wang
Jian-Feng
JF
Hu
Zhi-Ping
ZP
Shen
Jian-Ping
JP
Gao
Rui-Lan
RL
Ye
Bao-Dong
BD
Lin
Shen-Yun
SY
Shen
Yi-Ping
YP
Chen
Jun-Fa
JF
Luo
Xiou-Su
XS
Zhou
Yu-Hong
YH
Yu
Rong-Xi
RX
D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D020298:U937 Cells
D000951:Antigens, Neoplasm; D037621:Artemisinins; D000077332:Artesunate