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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 TCRζ levels are a common characteristic of patients with leukemia, and upregulating TCRζ could partially recover T cell function. In this study, we characterized the effect of the stimulating factor induction on the TCRζ, Zap-70, and FcɛRIγ levels, IFN-γ secretion, and the distribution and clonal expansion of TCR Vβ 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 TCRζ and Zap-70 levels with deceased FcɛRIγ 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-γ 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 Vβ subfamily T cells expressed was increased; however, all of the TCR Vβ 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 TCRζ and Zap-70 and recovery of the TCR Vβ repertoire in AML patients. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory and degenerative disorder of the central nervous system. The measles virus (MV) and host and environmental factors are involved in the development of SSPE , but the precise mechanism by which the MV causes SSPE is still unknown. Studies have indicated that in SSPE patients, specific polymorphisms of certain genes are most likely involved in impairing the host's ability to eradicate the MV. The purpose of our study was to elucidate the role of polymorphisms in the genes encoding interleukin (IL)-2, IL-18, and tumor necrosis factor alpha (TNF-α) in the development of SSPE. Using the polymerase chain reaction with sequence-specific primers, the single-nucleotide polymorphisms (SNPs) of the promoter regions of IL-2 (−330), TNF-α (−308), and IL-18 (−137 and −607) were studied in 54 patients with SSPE and 72 healthy controls. The frequency of SSPE patients with the AA genotype of IL-18 at position −607 was significantly higher than the frequency of those with the CC genotype ( p<0.001, odds ratio [OR]: 5.76), and a significantly higher proportion of patients had the C allele at −137 compared with the controls ( p=0.002, OR: 2.72). In a haplotype analysis of two SNPs in the IL-18 gene, the frequency of the CA haplotype was significantly higher in SSPE patients ( p<0.001, OR: 3.99) than in the controls. The IL-2 (−330) and TNF-α (−308) polymorphisms revealed no significant differences. In conclusion, these data suggest that the IL-18 gene polymorphisms at position −607 and −137 might be genetic risk factors for the SSPE disease. Two SNPs of the IL-18 gene were higher in SSPE patients than in controls. There was no difference between patients and controls in IL-2 or TNF-α polymorphisms in SSPE frequency. [ABSTRACT FROM AUTHOR]

T-cell immunodeficiency is a common feature in patients with chronic myeloid leukemia (CML), and deficiency in CD3 levels was detected in T cells from these patients, which may represent a characteristic that is related to a lower T cell activation. In this study, we explored the possibility that forced TCRζ gene expression may upreg-u-late T cell receptor (TCR) signaling activation and reverse interleukin-2 (IL-2) production in T cells from patients with CML. A recombinant eukaryotic vector expressing TCRζ was transfected into T cells by nucleofection. Phosphorylated TCRζ, phosphorylated NF-κB, and the IL-2 level in TCRζ-transfected CD3+T cells that were activated with anti-CD3 and anti-CD28 antibodies were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). Significantly increased TCRζ levels were found in TCRζ-transfected CD3+T cells. After CD3 and CD28 antibody stimulation, a significantly higher phosphorylated TCRζ chain level was demonstrated, and an increased IL-2 production in TCRζ-upregulated T cells was associated with the increased expression of the phosphorylated NF-κB. In conclusion, TCRζ gene transfection could restore TCRζ chain deficiency and enhance IL-2 production in T cells from patients with CML. It is possible that TCRζ chain reconstitution in leukemia-specific, clonally expanded T cells will effectively increase their activation of antileukemia cytotoxicity. One chain of the T cell receptor TCRζ was overexpressed in CD3+T cells and following activation of those cells by antibody, the gene product was observed to be phosphorylated. The Ab-stimulated T cells produced more IL-2 and also had more activated NF-κB. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and chemical carcinogen exposure, genetic susceptibility has been reported to play a key role in the development of this disease. Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with NPC in a Chinese population. We analyzed single-nucleotide polymorphisms of IL-2 gene −330 T/G and +114 T/G in 180 patients with NPC and 200 age- and sex-matched controls, using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods, and serum IL-2 levels were measured by enzyme-linked immunosorbent assay. Serum IL-2 levels were decreased in patients with NPC compared with controls ( p < 0.01). There were significant differences in the genotype and allele frequencies of IL-2 gene −330 T/G polymorphism between the group of patients with NPC and the control group ( p < 0.05). Moreover, genotypes carrying the IL-2 −330 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in patients with NPC. Carrying the IL-2 −330 G variant allele was associated with a decreased ability to produce IL-2, which may contribute to NPC susceptibility. [ABSTRACT FROM AUTHOR]