Article

Decreased level of recent thymic emigrants in CD4+ and CD8+T cells from CML patients

Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
Journal of Translational Medicine (Impact Factor: 3.99). 05/2010; 8:47. DOI: 10.1186/1479-5876-8-47
Source: PubMed

ABSTRACT T-cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor. Based on our previous finding, to further characterize the immune status, T cell proliferative history was analyzed in CD4+ and CD8+ T cells from chronic myeloid leukemia (CML) patients.
Quantitative analysis of deltaRec-psiJalpha signal joint T cell receptor excision circles (sjTRECs) was performed in PBMCs, CD3+, CD4+ and CD8+T cells by real-time PCR, and the analysis of 23 TRBV-D1 sjTRECs was performed by semi-nested PCR. Forty eight CML cases in chronic phase (CML-CP) were selected for this study and 17 healthy individuals served as controls.
The levels of deltaRec-psiJalpha sjTRECs in PBMCs, CD3+, CD4+, and CD8+ T cells were significantly decreased in CML patients, compared with control groups. Moreover, the numbers of detectable TRBV subfamily sjTRECs, as well as the frequency of particular TRBV-BD1 sjTRECs in patients with CML were significantly lower than those from healthy individuals.
We observed decreased levels of recent thymic emigrants in CD4+ and CD8+ T cells that may underlay the persistent immunodeficiency in CML patients.

Download full-text

Full-text

Available from: Grzegorz K Przybylski, Jun 19, 2015
0 Followers
 · 
155 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A previous study has demonstrated a significant decrease in the TCRzeta gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRzeta-regulating factors, the distribution of the TCRzeta 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcepsilonRIgamma and ZAP-70 genes. TCRzeta 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCRzeta, FcepsilonRIgamma, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRzeta gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIgamma and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCRzeta 3'-UTR and alternatively splieced (AS) TCRzeta 3'-UTR which have been alternatively splieced in the WT TCRzeta 3'-UTR . However, 35% of the CML cases contained only the wild type TCRzeta 3'-UTR isoform. Based on the TCRzeta 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT+AS- CML group, containing patients that express only the wild type TCRzeta 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCRzeta 3'-UTR isoforms. A significantly different ASF/SF-2 and FcepsilonRIgamma gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCRzeta expression may be characterized in the WT+AS-and WT+AS+CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCRzeta [unknown]3'-UTR, is thought to participate in feedback regulation. The characteristics of TCRzeta 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.
    Journal of Hematology & Oncology 12/2012; 5(1):74. DOI:10.1186/1756-8722-5-74 · 4.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-kappaB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p < 0.0001); however, the expression level of MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-kappaB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-kappaB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.
    Cancer Cell International 04/2013; 13(1):37. DOI:10.1186/1475-2867-13-37 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.
    Journal of Hematology & Oncology 09/2013; 6(1):74. DOI:10.1186/1756-8722-6-74 · 4.93 Impact Factor