Upregulated TCRζ Enhances Interleukin-2 Production in T-Cells from Patients with CML

Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Shi, Li; Li, Bo; Wu, Xiuli; Lu, Yuhong; Li, Yangqiu

doi:10.1089/dna.2012.1798

Cited by 16 publications

(19 citation statements)

References 35 publications

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“…The TCRf chain is considered to be a limiting factor for the assembly and transport of the complex to the cell surface, which is crucial for receptor signaling functions as it provides 6 of 10 immunoreceptor tyrosinebased activation motifs (ITAMs) for the complex (Call and Wucherpfennig, 2005;Li, 2008;Zha et al, 2012a). TCRf chain tyrosine phosphorylation is the first step in the signal transduction cascade initiated after TCR/CD3 engagement followed by phosphorylation of the cellular substrate ZAP-70 (TCRf chain-associated protein kinase 70 kDa), a cytosolic protein.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma

Liao

Zhou

Wang

et al. 2015

DNA and Cell Biology

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Section: Introductionmentioning

confidence: 99%

Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma

Liao

Zhou

Wang

et al. 2015

DNA and Cell Biology

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“…Therefore, enhancing CD3 expression may reactive the T cell activation functions and reverse the immunodeficiency in leukemia patients. Enhancement in TCRz (CD3z), which is crucial for TCR signaling functions, because it provides 6 of 10 immunoreceptor tyrosine-based activation motifs for the TCR-CD3 complex (Call and Wucherpfennig, 2005;Li, 2008;Zha et al, 2012a), was reported by different methods, including cytokine induction and TCRz transfer in T cells of CML patients (Chen et al, 2009;Zha et al, 2012b). A previous study showed that IL-2 could enhance the TCRf level, but it could not completely recover the TCRf level in T cells in CML patients (Chen et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…T cells from patients with leukemia are functionally impaired, and this is related to a decrease in the TCRz chain expression (Chen et al, 2000;Fischer et al, 2005;Li, 2008;Chen et al, 2011). Recently, we have reported significantly lower expression of TCRf in patients with AML and CML, and increasing TCRz expression by gene transfer enhances the activation and cytotoxicity of T cells from patients with CML (Chen et al, 2009;Zha et al, 2012aZha et al, , 2012b. However, there are few data characterizing TCRz upregulation and the T cell activation and proliferation induced by different methods such as gene transfer and cytokine induction in T cells from AML.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction

Shi

Chen

Zha

et al. 2015

DNA and Cell Biology

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Defective T cell receptor (TCR) signaling resulting in lower T cell function plays a crucial role in the pathogenesis of T cell immunodeficiency in leukemia. Previous studies have indicated that lower TCRf levels are a common characteristic of patients with leukemia, and upregulating TCRz could partially recover T cell function. In this study, we characterized the effect of the stimulating factor induction on the TCRf, Zap-70, and FceRIc levels, IFN-g secretion, and the distribution and clonal expansion of TCR Vb subfamilies in CD3 + T cells sorted from peripheral blood from acute myeloid leukemia (AML) patients. The induction included single stimulating factor or a combination with different cytokines (IL-2, IL-7, IL-2 + IL-7, IL-7 + IL-12, CD3, CD3 + CD28 antibody, CD3 + CD28 antibody + IL-2, and CD3 + CD28 antibody + IL-7) at 72 h. The results showed that increased TCRf and Zap-70 levels with deceased FceRIc in T cells after induction, and different responses to cytokine in T cell from different cases may indicate the heterogeneity of T cells and different immune statuses in different AML cases. Increased IFN-g levels in T cells from AML patients were detected after induction in the IL-12 + IL-7, CD3 + CD28 + IL-2, and CD3 + CD28 + IL-7 groups. Moreover, the number of TCR Vb subfamily T cells expressed was increased; however, all of the TCR Vb subfamily T cells in the AML patients could not be completely recovered after induction. In conclusion, the cytotoxicity and activation function of T cells could be enhanced after induction by different stimuli accompanied by an increase in TCRf and Zap-70 and recovery of the TCR Vb repertoire in AML patients.

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“…Cells were collected by centrifugation and resuspended at 2.5 · 10 6 cells for Molt-4 and Jurkat cells per 100 mL of the appropriate NucleofectorÔ kit solution (Amaxa Biosystems) (Huang et al, 2011;Chen et al, 2012;Zha et al, 2012). Malignant T cells were nucleofected with 3 mg of PPP2R5C-siRNAs or a control nonsilencing scrambled (SC) siRNA using the C-005 (Molt-4 cells) or X-001 ( Jurkat cells) program of the Nucleofection Device II (Amaxa Biosystems).…”

Section: Nucleofectionmentioning

confidence: 99%

Differential Gene Expression Profiles of PPP2R5C-siRNA-Treated Malignant T Cells

Chen

Liu

Shen

et al. 2013

DNA and Cell Biology

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Recently, alterations in the expression pattern of PPP2R5C associated with malignant transformation have been characterized, and PPP2R5C overexpression was demonstrated in leukemias. To confirm the role of PPP2R5C in proliferation and its molecular mechanism, three PPP2R5C-siRNAs and a scrambled nonsilencing siRNA control were used to treat Molt-4 and Jurkat T cells. After nucleofection, PPP2R5C expression and biological consequences based on a highly efficient and specific PPP2R5C-siRNA were demonstrated by qRT-PCR, CCK-8 assay, Annexin V/PI, and flow cytometry. The global gene expression profile of PPP2R5C-siRNA-treated Jurkat T cells was established. A significant reduction in the PPP2R5C mRNA level was observed at 24 to 72 h in Molt-4 and Jurkat T cells with all of the PPP2R5C-siRNAs. The proliferation rate of Molt-4 and Jurkat T cells transfected with different PPP2R5C-siRNAs was significantly decreased at 72 h compared with the control ( p < 0.05). However, the transfected cells did not show a significant increase in Annexin V/PI-positive cells (apoptosis). The highly efficient PPP2R5C-siRNA2 was used to treat Jurkat T cells for gene expression profile analysis. In total, 439 genes were upregulated, and 524 genes were downregulated at least twofold in PPP2R5C-siRNA-treated Jurkat T cells. Changes in signaling pathway genes closely related to the TCR, Wnt, calcium, MAPK, and p53 signaling pathways were observed. In conclusion, the suppression of PPP2R5C by RNA interference could effectively inhibit the proliferation of leukemic T cells, the PPP2R5C-siRNA treatment altered gene expression profiles, and the differential expression of the glycogen synthase kinase 3 beta (GSK-3b), ataxia telangiectasia mutated (ATM), and Mdm2 p53 binding protein homolog (MDM2) genes may play an important role in the effects of PPP2R5C knockdown in Jurkat T cells.

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Upregulated TCRζ Enhances Interleukin-2 Production in T-Cells from Patients with CML

Cited by 16 publications

References 35 publications

Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma

Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma

Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction

Differential Gene Expression Profiles of PPP2R5C-siRNA-Treated Malignant T Cells

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