Mechanism of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 mediated anti-neoplastic effects of cytokine-induced killer cells
- Author:
- No author available
- Journal Title:
- JOURNAL OF LEUKEMIA & LYMPHOMA
- Issue:
- 1
- DOI:
- 10.3760/cma.j.issn.1009-9921.2011.01.007
- Key Word:
- 淋巴细胞功能相关抗原1;胞间黏附分子1;DC-CIK;GATA3转录因子;T-bet基因;Lymphocyte function-associated antigen-1;Intercellular adhesion molecule-1;DC-CIK;GATA3 transcription factor;T-bet gene
Abstract： Objective To investigate the molecular mechanism underlying lymphocyte functionassociated antigen-1 (LFA-1) / intercellular adhesion molecule-1 (ICAM-1) mediated anti-neoplastic effects of cytokine induced killer (CIK) cells. Methods Lymphocytes isolated from peripheral blood of children leukemia were induced with interferon-gamma (IFN-y), anti-CD3 monoclonal antibody (CD3McAb) and interleukin-2 (IL-2) and co-cultured with dendrite cells (DC) to generate DC-CIK cells. When treated with LFA-1 monoclonal antibody, cytotoxicity of DC-CIK cells against leukemia cell lines was measured by the MTT assay, while RT-PCR and Western blotting were used to determine mRNA and protein expressions of GATA-3 and T-bet in DC-CIK cells, respectively. IL-12, IFN-γ and tumor necrosis factor-α (TNF-α) levels released by DC-CIK cells were quantified by ELISA. Results Induced DC-CIK cells were regular, round and transparent with variable cell volume and cellular aggregation. When treated with mouse anti-human LFA-1 monoclonal antibody, the cytotoxicity decreased mostly towards B95 cells under administration of 20 μg/ml LFA-1 monoclonal antibody in comparison with the control group(t =10.138, P ＜0.05). It led to a highest elevation of GATA-3 mRNA and protein levels (t =16.386, P ＜ 0.05; t =22.652, P ＜ 0.05) and a most decrease of T-bet mRNA and protein levels (t =17.728, P ＜0.05; t =17.452, P ＜0.05) under 20 μg/ml LFA-1 monoclonal antibody in B95 cells group in comparison with the control group. The expression levels of IL-12,IFN-γ, and TNF-o in supernatant were the lowest under 20 μg/ml LFA-1 monoclonal antibody in B95 cells group in comparison with the control group (t =21.621, P ＜0.05; t =13.739, P ＜0.05; t =15.278, P ＜0.05).Conclusion GATA-3 and T-bet were implicated in the LFA-1/ICAM-1 mediated anti-neoplastic effects of DC-CIK cells via activation of the Th1 pathway, with high secretion of Th1 cytokines, such as IL-12, IFN-γ and TNF-α.
- [1]韩根成,沈倍奋.Th17细胞分化、调节及效应研究进展[J].2008,(2).
- [2]张春霞,任少敏.T-bet/GATA3与疾病[J].2008,(3).
- [3]王强,冀朝晖,李若瑜.T-bet/GATA3对Th1/Th2分化的调节及其与疾病的关系[J].2005,31(3).
- [4]赵卫东,凌斌.GATA-3与Th1/Th2的分化[J].2007,(18).
- [5]Kim MJ,Ahn SC,Yeom SR,etc.Quercetin regulates Th1/Th2 balance in a murine model of asthma.[J].2009,9(3).
- [6]Hui KM,Ng LH,Yong HX,etc.Characterization of the recognition and functional heterogeneity exhibited by cytokine-induced killer cell subsets against acute myeloid leukaemia target cell.[J].2009,126(3).
- [7]Satoshi, Koida,Kunihiro, Tsukasaki,Takeshi, Tsuchiya,etc.Primary T-cell lymphoma of the thyroid gland with chemokine receptors of Th1 phenotype complicating autoimmune thyroiditis.[J].2007,92(3).
- [8]Lee Y,Shim HJ,Park DC.Expression of GATA3, T-bet, IL-4, and IFN-gamma mRNA in the effusion of OME patients.[J].2009,73(8).
- [9]Finotto S.T-cell regulation in asthmatic diseases.[J].2008,94(0).
- [10]Frisullo G,Nociti V,Iorio R.T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity.[J].2009,158(1).
- [11]Lam KP,Wong SC,Tan AH,etc.T helper cell-specific regulation of inducible costimulator expression via distinct mechanisms mediated by T-bet and GATA-3.[J].2008,283(1).
- [12]Rojas R,Saravia NG,Valderrama L,etc.T-bet, GATA-3, and Foxp3 expression and Th1/Th2 cytokine production in the clinical outcome of human infection with Leishmania (Viannia) species.[J].2010,202(3).
- [13]Chang CH,Sofi MH,Li W,etc.Elevated IL-6 expression in CD4 T cells via PKCtheta and NF-kappaB induces Th2 cytokine production.[J].2009,46(7).
- [14]Radbruch A,Panse I,Bergthaler A,etc.Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.[J].2010,32(1).
- [15]Wakui H,Komatsuda A,Iwamoto K.GATA-3 is upregulated in peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome.[J].2009,71(6).
- [16]Mariani L,Schulz EG,Radbruch A,etc.Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12.[J].2009,30(5).
- [17]Hou W,Cheng Y,Zhang J.Immunoregulatory effects of sinomenine on the T-bet/GATA-3 ratio and Th1/Th2 cytokine balance in the treatment of mesangial proliferative nephritis.[J].2009,9(7).
- [18]Heath H,Bergen I,Grosveld F,etc.Critical role for the transcription regulator CCCTC-binding factor in the control of Th2 cytokine expression.[J].2009,182(2).
- [19]Ribeiro de Almeida C,van Hamburg JP,de Bruijn MJ.Gene expression profiling in mice with enforced Gata3 expression reveals putative targets of Gata3 in double positive thymocytes.[J].2009,46(16).
- [20]Kang JS,Yang KH,Kim Y,etc.Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma.[J].2007,7(13).