The Feature of TCR Zeta Gene in CD4+ and CD8+ T Cells in Patients with CML.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4526-4526
Author(s):  
Si Chen ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Xiuli Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Gene Expression Level ◽  
Expression Level ◽  
Chain Gene ◽  
Zeta Chain ◽  
Normal Individuals ◽  
Normal Controls

Abstract The T-cell receptor (TCR) zeta chain is a master sensor and regulator of lymphocyte responses which plays a critical role in TCR-mediated signal transduction. The abnormal expression of TCR zeta gene was found in some malignancies and immune disease. Cellular immune deficiency is the common feature in patients with chronic myeloid leukemia (CML). Our previous studies had showed that 60% of CML patients displayed an abnormally low expression of TCR zeta chain in peripheral blood mononuclear cells (PBMCs). To further estimate the changes of zeta chain expression of T-lymphocyte subsets in CML, TCR zeta chain gene expression level in purified CD4+ and CD8+ T cells sorted by MACS were detected by real-Time PCR with SYBR Green I technique, CD4+ and CD8+ T cells from both 10 cases with CML and 10 normal individuals were selected to analyze in the study. β2 -microglobulin was used as an endogenous reference. Relative changes in TCR zeta gene expression level were used by the 2−ΔCt×100% method. The relative mRNA expression level of TCR zeta gene in CD4+ and CD8+ T cells from CML was 4.06±4.82% and 3.82±4.25% respectively, whereas 7.75±2.52% and 5.19±1.25% were found in normal individuals. There was a wide range in the TCR zeta gene expression level of CD4+ T cells from CML patients (0.23–15.93%,) with a median value of 1.77%, whereas the a range of (4.74–12.81%) with a median of 7.93% was showed in normal controls (P=0.046). The expression level of TCR zeta gene in CD8+ T cells from controls ranged from 3.47% to 6.75% (median 5.52%) and in CML patients from 0.86% to 15.55% with a median of 2.51% (P=0.340). The results indicated that, compared with normal controls, zeta chain gene expression was obviously down-regulated in CD4+ T cells from patients with CML. However, there was not significant different in expression level of TCR zeta gene of CD8+ T cells between CML patients and normal individuals. Moreover, the expression level of TCR zeta gene is nonsignificant age-associated or gender-link in CD4+ T cells and CD8+ T cells from patients with CML. In conclusions, the results provide at first the difference of TCR-zeta gene expression pattern in CD4+ and CD8+ T cells from patients with CML, this may be reflective of signaling difference between the different T cell subtypes in immunodeficiency state of patients.

Expression Pattern of TCR-zeta Chain in Patients with Aplastic Anemia and Polycythemia Vera.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3763-3763
Author(s):  
Lijian Yang ◽  
Yangqiu Li ◽  
Chuang Li ◽  
Shaohua Chen ◽  
Si Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Aplastic Anemia ◽  
Polycythemia Vera ◽  
Expression Pattern ◽  
Gene Expression Pattern ◽  
Gene Expression Level ◽  
Expression Level ◽  
Chain Gene ◽  
Zeta Chain

Abstract TCR zeta chain of TCR-CD3 receptor complex is though to be critical for T cells development and T cell effector function. The absence of TCR zeta chain not only influences the TCR expression on the cell membrane, but also impairs the proliferative response and the level of activation of mature T cells. Recently, the abnormal expression of TCR zeta chain was found different disease, for example in hematological malignancy. In the present study, we analyzed the expression level of TCR zeta chain gene in T cells from patients with aplastic anemia (AA) and polycythemia vera (PV), thereby to estimate the feature of T cells activation status. Real-time PCR with SYBR Green I technique was used for detecting the expression level of TCR zeta chain gene in peripheral blood mononuclear cells of patients with AA (25 cases),PV (12 cases), and 30 normal individuals. β2-microglobulin gene was used as an endogeneous reference. Evaluation of TCR zeta chain gene expression level were used the 2−ΔΔCt method. Compared with the normal control, TCR zeta chain gene expression level could be divided into two groups: 10 patients with AA (40%) and 5 patients with PV (41.7%) were over expression, while 15 patients with AA (60%) and 7 patients with PV (58.3%) were down expression. The expression level of TCR zeta gene is nonsignificat age-associated in both AA and PV patients. Moreover, the expression level of TCR zeta gene is nonsignificant age-associated or gender-link in T cells from patients with AA. The signaling pathway of T cells activation might display some disorder in patients with AA or PV. The effect of the change of TCR zeta chain gene expression pattern in AA and PV patients should be further confirmed.

CD3-Zeta Gene Expression in Workers Benzene-Exposed and Benzene- Poisoned Workers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4925-4925
Author(s):  
Bo Li ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Wei Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Mononuclear Cells ◽  
Skewed Distribution ◽  
Gene Expression Level ◽  
Expression Level ◽  
Peripheral Blood Mononuclear ◽  
Invariant Structure ◽  
Normal Individuals ◽  
Exposed Workers

Abstract Benzene is an industrial chemical and component of cigarette smoke, gasoline, and automobile emissions. Benzene’s toxic effects on the blood and bone marrow can induce aplastic anemia and leukemia. Benzene is known to be highly toxic to a variety of cell types including lymphocytes. Our previous study showed that skewed distribution and clonal expansion of TCR Vα subfamily T cells had been found in benzene-exposed workers, indicating that the disorder of T cell immune function might relate to benzene-exposed. The TCR expressed on the surface of T cells is associated with an invariant structure-CD3 and composed the TCR/CD3 complex. The CD3ζ chain plays an important role in the complex which involved in signal transduction. Little is known about the feature of CD3 ζ chain expression in benzene-exposed workers. To further identify the expression level of CD3 ζ gene in benzene-exposed workers, real-time PCR with SYBR Green±technique was used for detecting CD3 ζ gene expression level in peripheral blood mononuclear cells from 29 benzene-exposed workers, 42 benzene-poisoned workers and 20 normal individuals. β2- microglobulin gene (β2M) was used as an endogenous reference. Relative changes in CD3 ζ gene expression level was used by the 2−ΔCt×100% method (ΔCt=Ct(ζ) −Ct(β2M) ). CD3ζ gene could be detected in all of normal individuals, however, only 21 out of 29 benzeneexposed workers could be detected the CD3ζ gene with a mean expression level of 15.0 ±24.9, and in 33 of all 45 benzene-poisoned workers with mean value of 19.8 ±29.7. The detectable CD3 ζ gene expression level in both benzene-exposed and benzene-poisoned groups increased significantly compared with that in normal individuals (3.00±2.11, P< 0.05). This is, to our knowledge, the first description of the effect of benzene-exposed on the expression of the CD3 ζ gene. The abnormality expression of CD3 ζ gene might lead to immune dysfunction in benzene-exposed and benzene-poisoned workers. In addition, CD3ζ gene could not be detected in a part of samples, whether the absence of CD3ζ gene might related to dysfunction of T cells in workers with benzene-exposed and benzenepoisoned, it remains an open question.

The Feature of TCR Vβ Repertoire, Thymic Recent Output Function and TCR-zeta Chain Expression in Patients with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2099-2099
Author(s):  
Xueli Zhang ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Si Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Immune Thrombocytopenic Purpura ◽  
Clonal Expansion ◽  
Expression Level ◽  
Chain Gene ◽  
Output Function ◽  
Thrombocytopenic Purpura ◽  
Normal Individuals

Abstract Chronic idiopathic/immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which antiplatelet antibodies induce destruction of platelets. T cells may play a critical role in controlling the synthesis of autoantibodies, and may relate to initiation of ITP. In order to identify the feature of T cells immune state in patients with ITP, TCR Vβ repertoire which can identify T cell proliferation in response to antigenic stimulation; signal joint T-cell receptor excision DNA circles (TRECs) which can use to estimate the thymic recent naïve T cells output function and the expression level of TCR ζ chain gene which defined as an important factor in T cells signaling. Specific Vβ family primers, RT-PCR and genescan technique were use to analyze the expression of TCR Vβ subfamily and the clonality of TCR Vβ T cells in cDNA form peripheral blood mononuclear cells (PBMCs) of 5 ITP patients; quantitative analysis of TRECs in DNA of PBMCs from 15 cases were preformed by real-time PCR (TaqMan); real-time PCR with SYBR Green I technique was used for detecting TCR ζ gene expression level in cDNA of PBMCs from of 18 patients, β2 -microglobulin gene was used as an endogenous reference, relative changes in TCR ζ chain gene expression level were used by the 2− ΔCt method. 25 normal individuals served as control. The results showed that only 4–11 Vβ subfamily T cells could be identified in ITP cases. The frequent expression Vβ subfamilies were Vβ2 (100%), Vβ3 (100%), Vβ19 (80%) and Vβ21 (80%), while it could not detected the expression of Vβ4, Vβ6–12, Vβ17, Vβ20 and Vβ24. However, all 24 Vβ subfamilies could be detected in samples from normal individuals and all of them displayed polyclonality, clonal expansion Vβ T cells could be found in some subfamilies in every patient. The frequent clonal expansion T cells were Vβ21 subfamily which could be identified in 4 out of 5 cases. The mean value of TRECs was 2.60±2.99 copies/1000 PBMCs in ITP patients, it was not significantly difference (p>0.05) in comparison with normal group (3.76±3.42 copies/1000 PBMCs), although the TRECs level displayed changefully in different patients with ITP. In four out of fifteen ITP cases no TRECs copies could be detected in more than 10000 PBMCs. The higher frequency of TRECs was found in female group, however it was not statistical significance in comparison with male group. The expression of TCR ζ chain gene could be detected in all of 25 normal samples, and TCR ζ gene was found in 17 out of 18 cases with ITP. However, the expression level of TCR ζ gene was lower in ITP samples than those from normal individuals (P=0.017). The expression level of TCR ζ gene is nonsignificat age-associated or gender-link in ITP patients. In conclusions, the restricted expression of TCR Vb subfamilies and clonal expanded Vβ T cells are the T-cell immune feature in ITP, and the frequent presentation of clonal expanded Vβ21 T cells may relate to the disorder of cellular immune function in ITP. At least, in most cases with ITP, the normal level of naïve T cells and thymic recent output function were detected. It is, to our knowledge, the first description in the expression feature of TCR ζ gene in ITP patients, which displayed down expression, it might be a feature in autoimmune disease.

A time dependent gene expression level of C3, C3aR and CTSL in CD4+ T cells

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1201
Author(s):  
Cecilie Bo Hansen ◽  
Anton Willer ◽  
Hanne Vibeke Hansen Marquart ◽  
Martin Kolev ◽  
Claudia Kemper ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd4 T Cells ◽  
Time Dependent ◽  
Gene Expression Level ◽  
Expression Level

scholarly journals Redox Imbalance in CD4+ T Cells of Relapsing-Remitting Multiple Sclerosis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammad Javad Tavassolifar ◽  
Abdorreza Naser Moghadasi ◽  
Behnaz Esmaeili ◽  
Omid Sadatpour ◽  
Mohammad Vodjgani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gene Expression Level ◽  
Expression Level ◽  
Related Factor ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients

As a prevalent autoimmune disease of the central nervous system in young adults, multiple sclerosis (MS) is mediated by T cells, particularly CD4+ subsets. Given the evidence that the perturbation in reactive oxygen species (ROS) production has a pivotal role in the onset and progression of MS, its regulation through the antioxidant molecules is too important. Here, we investigated the level of the redox system components in lymphocytes and CD4+ T cells of MS patients. The study was performed on relapsing-remitting MS (RRMS) patients ( n = 29 ) and age- and sex-matched healthy controls ( n = 15 ). Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated by anti-CD3/CD28. The level of ROS, anion superoxide (O2-), and L-𝛾-glutamyl-Lcysteinylglycine (GSH) was measured by flow cytometry in lymphocytes/CD4+ T cells. The gene expression level of gp91phox, catalase, superoxide dismutase 1/2 (SOD), and nuclear factor-E2-related factor (Nrf2) was also measured by real-time PCR. We found that lymphocytes/CD4+ T cells of RRMS patients at the relapse phase significantly produced higher levels of ROS and O2- compared to patients at the remission phase ( P value < 0.001) and healthy controls ( P value < 0.001 and P value < 0.05, respectively). Interestingly, the gene expression level of gp91phox, known as the catalytic subunit of the NADPH oxidase, significantly increased in MS patients at the relapse phase ( P value < 0.05). Furthermore, the catalase expression augmented in patients at the acute phase ( P value < 0.05), while an increased expression of SOD1 and Nrf2 was found in RRMS patients at relapse and remission phases ( P value < 0.05). The increased production of ROS in CD4+ T cells of RRMS patients highlights the importance of amplifying antioxidant components as an efficient approach to ameliorate disease activity in MS patients.

scholarly journals c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Have Distinct Roles in CD8+ T Cell Activation

2002 ◽  
Vol 195 (7) ◽  
pp. 811-823 ◽  
Author(s):  
Dietrich Conze ◽  
Troy Krahl ◽  
Norman Kennedy ◽  
Linda Weiss ◽  
Joanne Lumsden ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Cell Surface Expression ◽  
Chain Gene ◽  
Α Chain

The c-Jun NH2-terminal kinase (JNK) signaling pathway is induced by cytokines and stress stimuli and is implicated in cell death and differentiation, but the specific function of this pathway depends on the cell type. Here we examined the role of JNK1 and JNK2 in CD8+ T cells. Unlike CD4+ T cells, the absence of JNK2 causes increased interleukin (IL)-2 production and proliferation of CD8+ T cells. In contrast, JNK1-deficient CD8+ T cells are unable to undergo antigen-stimulated expansion in vitro, even in the presence of exogenous IL-2. The hypoproliferation of these cells is associated with impaired IL-2 receptor α chain (CD25) gene and cell surface expression. The reduced level of nuclear activating protein 1 (AP-1) complexes in activated JNK1-deficient CD8+ T cells can account for the impaired IL-2 receptor α chain gene expression. Thus, JNK1 and JNK2 play different roles during CD8+ T cell activation and these roles differ from those in CD4+ T cells.

scholarly journals Single-Cell RNA Sequencing Unveils the Hallmarks of Populations at Different Stages of HTLV-1 Infection

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3323-3323
Author(s):  
Yan Huang ◽  
Peifang Jiang ◽  
Jiazheng Li ◽  
Yanxin Chen ◽  
Zhengjun Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cd4 T Cells ◽  
Treg Cells ◽  
Cd4 T Cell ◽  
Expression Level ◽  
Normal People ◽  
Healthy Donors

Abstract Background Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature T-cell neoplasm caused by human T -cell leukemia virus type 1 (HTLV-1). Up to 5% of infected individuals develop to ATL. HTLV-1 preferentially infects CD4 + T cells, and stimulates cell proliferation and prevents cell death by apoptosis. The viral oncogene-encoded proteins, Tax and HBZ, play important roles in viral infection and cell immortalization. However, the host factor of developing from carrier to patient is not clear. Results To characterize the heterogeneity of ATL patients, we performed single-cell RNA-sequencing (10x Genomics) analysis on single cell suspensions isolated from PBMCs of nine samples, including three ATL patients, three HTLV-1 asymptomatic carriers as well as three healthy donors (HD). We acquired 82977 high-quality cells with a median of 1718 genes detected per cell. Unsupervised clustering using Seurat followed by visualization in t-Stochastic Neighbor Embedding (t-SNE) identified 29 distinct cell clusters (Figure 1A). The single cell profiling of ATL patients were significantly different from that of carriers and healthy donors, while the latter two had little difference (Figure 1B). Based on singleR packages and marker genes of each cluster, 4 major cell populations (T cells, NK cells, B cells and myeloid cells) and other rare cell types were annotated, such as erythrocyte cluster and eosinophils cluster. We observed an enrichment of CD4 + T cell from patients in 4 cluster (Figure 1C), which proportion of cells was higher than that of carriers and healthy donors. According to cell type annotation, cells from cluster 11 were CD4 + CD25 + Foxp3 + Treg cells. Based on the increasing proportion of cluster 11 in healthy people, carriers and patients, without significant statistical differences, we assumed that Foxp3 + Treg cells were involved in the evolution of ATL tumor cells. That was identical with published literatures. To investigate the differences between tumor and normal CD4 + T cell, the gene expression was compared among 7 clusters of CD4 + T cell from three groups. Using a threshold of p value &lt; 0.05 and | fold change| &gt;2. Through integrated analysis, we identified 26 commonly upregulated genes (gene expression level: patients &gt; carriers &gt; HD) and 9 downregulated genes (gene expression level: patients &lt; carriers &lt; HD. To further analyze the biological function of the common DEGs, gene ontology (GO) analysis showed that these genes could be mainly categorized into plasma membrane and protein binding. Subsequently, we validated the mRNA expression level of upregulated common DEGs among three groups by qRT-PCR. The isolated CD4 + T cell using CD4 microbeads of a total of 6 patients, 3 carriers and 9 normal specimens were included. The result showed that the mRNA expression levels of gene CADM1 and RGS13 in patients were higher than those in carriers and healthy donors, although there was no statistical difference between patients and carriers, and the expression levels of carriers tended to be higher than those in normal people (Figure 1D and E). Previously, CADM1 has been revealed to be highly expressed in HTLV-1-infected CD4 + T cells. Our study confirmed this result by single-cell profiling. RGS13, a member of the regulators of G protein signaling (RGS) family, participates in cellular communication. The role of RGS13 in ATL needs to be investigated. Conclusions This study is the first time to analyze the single-cell RNA level of ATL patients, HTLV-1 virus carriers and normal people. The peripheral blood cell composition of the patient is significantly different from that of the carriers and healthy donors, while it is similar between carriers and normal people. CD4 + T cells are the main cell population of patients. The proportion of CD4 + CD25 + Foxp3 + Treg cells increased gradually in healthy people, carriers and patients. DEGs analysis showed that CADM1 and RGS13 were highly expressed in CD4 + T cells of patients, followed by carriers, validated by 18 clinical samples. However, the molecular mechanism of RGS13 in the process from HTLV-1 infection to ATL needs to be further studied. Figure 1 Figure 1. Disclosures Hu: Astellas Pharma, Inc.: Research Funding.

scholarly journals Differential transcription directed by discrete gamma interferon promoter elements in naive and memory (effector) CD4 T cells and CD8 T cells.

1997 ◽  
Vol 17 (1) ◽  
pp. 199-208 ◽  
Author(s):  
T M Aune ◽  
L A Penix ◽  
M R Rincón ◽  
R A Flavell
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Transcriptional Activity ◽  
Memory T Cells ◽  
Gamma Interferon ◽  
Ifn Gamma ◽  
Naïve T Cells

Acquisition of the ability to produce gamma interferon (IFN-gamma) is a fundamental property of memory T cells and enables one subset (T helper 1 [TH1]) to deliver its effector functions. To examine regulation of IFN-gamma gene expression in a model system which recapitulates TH1 differentiation, we prepared reporter transgenic mice which express the luciferase gene under the control of proximal and distal regulatory elements (prox.IFN gamma and dist.IFN gamma) from the IFN-gamma promoter. Memory T cells, but not naive T cells, secreted IFN-gamma and expressed both prox.IFN gamma and dist.IFN gamma transcriptional activities. Naive T cells required priming to become producers of IFN-gamma and to direct transcription by these elements. While both CD4+ and CD8+ T cells produced IFN-gamma, only CD4+ T cells expressed prox.IFN gamma transcriptional activity. Induction of transcriptional activity was inhibited by known antagonists of effector T-cell populations. Cyclosporin A inhibited transcriptional activity directed by both elements in effector T cells. Elevated cyclic AMP inhibited transcriptional activity directed by prox.IFN gamma in primed CD4+ T cells but enhanced transcriptional activity directed by dist.IFN gamma in primed CD8+ T cells. Taken together, these data show that prox.IFN gamma and dist.IFN gamma transcriptional activities mirror IFN-gamma gene expression in naive and memory CD4+ T cells but suggest that differences exist in regulation of IFN-gamma gene expression in CD4+ and CD8+ T-cell subsets.

scholarly journals ABCA1, TCF7, NFATC1, PRKCZ and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Infante ◽  
M Franzese ◽  
A Ruocco ◽  
C Schiano ◽  
O Affinito ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Acute Coronary Syndrome ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Molecular Data ◽  
Aberrant Methylation ◽  
National Budget ◽  
Coronary Syndrome ◽  
Differentially Methylated Genes

Abstract Background Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease and the leading cause of death worldwide. Purpose To perform an epigenome-wide analysis in circulating CD4+ and CD8+ T cells of ACS patients and healthy subjects (HS) enrolled in the DIANA clinical trial (NCT04371809) in order to identify differentially methylated genes (DMGs). Methods Genomic DNA was extracted from CD4+ and CD8+ T cells of all subjects and sequenced by the reduced representation bisulfite sequencing (RRBS) platform. Functional pathway analysis was performed and significant DMGs were selected for gene expression validation by qRT-PCR in ACS patients and HS. GeneMANIA was used to built a prediction gene network. Correlation analyses between molecular data and clinical variables were performed. Results In CD4+ T cells we identified 61 differentially methylated regions (DMRs) associated to 57 annotated genes of which 53% (n=32) were hyper- and 47% (n=29) were hypo-methylated in ACS patients vs HS. In CD8+ T cells we identified 613 DMRs associated to 569 annotated genes of which 28% (n=173) were hyper- and 72% (n=440) were hypo-methylated between two groups. In both cell type of ACS patients, 175 DMRs were associated to 157 annotated genes of which 41% (n=72) were hyper- and 59% (n=103) were hypo-methylated. From functional analysis, we selected the top 5 DMGs in the prevalent pathways with the highest differential of methylation values. Specifically, we considered 6 hub genes: NFATC1, TCF7, PDGFA, PRKCB, PRKCZ and ABCA1 and determined their respective expression levels by q-RT-PCR. We found a significant up-regulation of the selected genes in ACS patients vs HS (P&lt;0.001 for all comparisons). Correlation analysis showed both common and cell specific correlation patterns. In CD4+ T cells, PDGFA promoter methylation was negatively correlated with CK-MB concentrations (r=−0.79, P=0.018). ABCA1, TCF7, PDGFA and PRKCZ gene expression was positively associated to CK-MB concentrations (r=0.75, P=0.03; r=0.760, P=0.029; r=0.72, P=0.044; r=0.74, P=0.035, respectively). Conlusions This study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells, providing specific methylation signatures that could help to clarify the role of aberrant methylation in ACS pathogenesis, and provide the basis for the search of novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health;Italian Ministry of Research and University

The Expression and Mechanism of Tim3 and PD-1 in Patients with Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4948-4948
Author(s):  
Caixia Li ◽  
Xiao Yu ◽  
Caihong Gu ◽  
Chao Ma ◽  
Hong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Heparin Anticoagulation ◽  
Ifn Γ ◽  
Normal Controls ◽  
Acute Myeloid

Abstract Objective: To investigatethe expression and the role of Tim3 and PD-1 on T cells of peripheral blood in patients with acute myeloid leukemia(AML). Consistently discuss the clinical significance of Tim3 and PD-1 co-expression on these cells and the mechanism of Tim3-mediated immune escape. Methods: Collectedclinical data of 36 patients who had been diagnosed with AML by bone marrow MICM classification, and then gathered their heparin anticoagulation peripheral blood before any treatment. The heparin anticoagulation peripheral blood from 20 healthy volunteers was gathered as normal control. We used the methods of immune fluorescence labeling and flow cytometry to detect expression of Tim3 on T cells. Then detected co-expression of Tim3 and PD-1 on T cells, consistently with IFN-γ secreting level on T cells. Results: 1.The proportions of CD4+ T cells and CD8+ T cells on lymphocytes in AML patients were (15.28±10.99)% and (9.19±7.54)% respectively, which were significantly lower than the proportion of normal controls [(31.12±2.22)% and (21.59±4.22)% respectively] (P<0.05). 2.The levels of Tim3 expression on CD4+ T cells and CD8+ T cells in AML patients were (4.77±3.560)% and (5.90±4.91)% respectively, which were significantly higher than the levels of normal controls [(0.73±0.62)% and (0.96±0.54)% respectively] (P<0.05). 3.Tim3 and PD-1 were co-expression on CD4+ T cells and CD8+ T cells in AML patients. 4.The IFN-γ secreting level in Tim3+ CD8+ T cells was significantly decreased than Tim3- CD8+ T cells (P<0.05). Conclusion: 1.The high expression of Tim3 on peripheral blood T cells in AML patients mediate T cell exhaustion/dysfunction, which can be an important mechanism of immune escape in leukemia. 2.PD-1 and Tim3 co-expression On CD4+ T cells and CD8+ T cells in AML patients which were dificient in there ability to produce IFN-γ. Further investigations are needed to explore the correlation of co-expression PD1 and Tim3 with process of AML, thus probably making Tim3 become another new immunotherapy target. Disclosures No relevant conflicts of interest to declare.

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