In Vitro Stimulation of Specific Antileukemia T-cell Response by Dendritic Cells Derived from CD14+ Acute Monocytic Leukemia Cells
10.3321/j.issn:1000-467X.2005.11.009
- VernacularTitle:CD14+单核细胞系白血病细胞来源树突细胞体外刺激特异抗白血病T细胞应答
- Author:
Li-Xia SHENG
1
;
Xiao-Bao XIE
;
Guo-Qiang QIU
;
Wei-Ying GU
;
Zhi-Lin WANG
;
Hao-Qing WU
Author Information
1. The Third Affiliated HospitalSoochow University
- Keywords:
Dendritic cells;
Leukemia,monocytic,acute;
CD14expression;
Antileukemia cytotoxic T-cell response
- From:Chinese Journal of Cancer
2005;24(11):1338-1344
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND & OBJECTIVE: Dendritic cells (DCs) or DClike cells had been successfully induced in vitro from leukemia cells, which may provide a promising immunotherapeutic protocol for leukemia. This study was designed to investigate the efficiency of in vitro generation of dendritic cells from CD14+ acute myelomonocytic (M4) or monocytic (M5) leukemia cells and their ability of stimulating specific antileukemia T-cell response.METHODS: Bone marrow mononuclear cells (BMMNCs) were isolated from 5M4/M5 leukemia patients with high CD14 expression, and then divided into 3groups: adherent leukemia cells, nonadherent blasts, and total unfractioned blasts. CD14 expression of the 3 groups was evaluated by flow cytometry (FCM). When cultured with or without granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-α) for 7-10 days, monocytic leukemia cell-derived dendritic cells (Mo-LDCs) were identified through morphologic observation and immunophenotype analysis using FCM. The immune function of Mo-LDCs was detected through allogeneic mixed lymphocyte reaction (Allo-MLR) and cytotoxicity assay of antileukemia cytotoxic T lymphocytes (CTLs). The leukemic origin of Mo-LDCs was confirmed by chromosomal karyotype analysis combined with the aberrant expression of myeloid antigens. RESULTS: The amount of CD14+ cells, which could differentiate into CD83+ mature DCs under induction of the cytokine combination, was higher in adherent leukemia cells than in nonadherent blasts and total unfractioned blasts. Regarding each 3 cell groups of the same patient or the unfractioned blasts of various patients, initial CD14 expression was positively related to the yield of CD83 + DCs after induction (r=0.967, P=0.007). Mo-LDCs exhibited typical morphology and phenotype as mature DCs, induced potent proliferation of homogeneous T cells in Allo-MLR, stimulated the expansion of leukemia-specific CTLs, and continued to possess the cytogenetic abnormalities of the original leukemia, as well as the aberrant expression of myeloid antigens. CONCLUSIONS: In M4/M5 subtype of AML, CD14+ cells could differentiate into immune-competent Mo-LDCs under the induction of the cytokine combination. CD14 expression level may predict the DCs differentiation ability of monocytic leukemia. MoLDCs, which possess the classical phenotype and function of DCs, as well as the abnormal leukemic antigens, may be useful for the immunotherapy of M4/M5 AML.
