ABSTRACT
Objective To detect the expressions of CD70 mRNA and protein and to determine the methylation status of CD70 gene promoter in T cells from patients with systemic lupus erythematosus (SLE).Methods Peripheral blood CD4+ and CD8+ T cells were isolated from 15 patients with active SLE,15 patients with inactive SLE and 15 healthy control subjects.Real-time quantitative reverse transcription-PCR was carried out to quantify the mRNA expression of CD70,flow cytometry to determine the frequency of CD4+CD70+ and CD8+ CD70+ T cells,and bisulfite sequencing to evaluate the methylation status of CD70 gene promoter in CD4+ and CD8+ T cells.Differences in these parameters among these groups were analyzed by one-factor analysis of variance and SNK-q test.Results Compared with the healthy controls,the patients with active SLE and inactive SLE showed a significant increase in CD70 mRNA expression in CD4+ T cells (0.82 ± 0.12 and 0.73 ± 0.11 vs.0.45 ±0.09,F =53.017,P ＜ 0.01) and in the frequency of CD70+CD4+ T cells (80.30％ ± 11.04％ and 66.80％ ± 3.98％ vs.12.48％ ± 3.45％,F =311.517,P ＜ 0.01).Also,the expression of CD70 mRNA in CD4+ T cells and the frequency of CD70+CD4+ T cells were significantly higher in patients with active SLE than in patients with inactive SLE (both P ＜ 0.05).There was a positive correlation between the frequency of peripheral CD70+CD4+ T cells and disease activity in SLE in these patients (r =0.792,P ＜ 0.01).The average methylation index of the region between-600 bp and-300 bp of CD70 gene promoter in CD4+ T cells was 0.32 ± 0.05 and 0.36 ± 0.05 respectively in the patients with active and inactive SLE,significantly lower than that in the healthy controls (0.62 ± 0.05,F =152.64,P ＜ 0.01),and the patients with active SLE showed a significantly lower methylation index than those with inactive SLE (P ＜ 0.05).Conclusions The CD70 gene promoter in CD4+ T cells is significantly hypomethylated in patients with SLE,which may directly lead to the overexpression of CD70.
ABSTRACT
CD70 is a member of TNFR (tumor necrosis factor receptor) super family, which is essential for maintaining immune response through controlling the activation, proliferation and differentiation of T cells and B cells. CD70 is highly expressed in various types of tumors which suggests that it may become a potentially effective target for immunotherapy. This paper summarizes the biological function and expression of CD70 in tumor tissues and the advances in research on the role of CD70 in antitumor therapy, so as to provide valuable references and evidence for the clinical application of CD70. Copyright © 2013 by TUMOR.
ABSTRACT
Objective To detect the expression of CD70 in peripheral T lymphocytes of patients with systemic lupus erythematosus (SLE) and the effect of azacitidine, an inhibitor of DNA methylation, on it. Methods Blood samples were obtained from 10 patients with active SLE (SLEDAI score ≥5), 10 patients with nonactive SLE (SLEDAI score < 5) and 10 normal human controls. Peripheral T lymphocytes were isolated and cultured for 72 hours. A part of the T lymphocytes from normal controls, which were cultured in the presence of azacitidine at 1 mol/L, served as the methylation-inhibited group. Semiquantitative reverse transcription PCR and flow cytometry were applied to detect the mRNA expression of CD70 and frequency of CD70+CD4+ cells in the cultured lymphocytes, respectively. Results The frequency of CD70+CD4+ lymphocytes was 14.55%±5.49% in normal control group, 85.25%±14.08% in active SLE group, 77.65% ±18.77% in nonactive SLE group, and 81.54%±8.71% in methylation-inhibited group. Compared with the normal control group, a significant increase was observed in both the frequency of CD70+CD4+ lymphocytes (all P < 0.01) and the expression of CD70 expression (all P < 0.05) in other three groups. There was a positive correlation between the frequency of peripheral CD70+CD4+ lymphocytes and disease activity of SLE in patients (r = 0.72, P < 0.05). Conclusions The elevated expression of CD70 appears to play a significant role in the immunologic disarrangement in SLE, and may act as a indicator of disease activity of this disease.