端粒缩短和复制潜能降低，这与系统性红斑狼疮患者中端粒酶阳性的CD8⁺CD28⁽低⁾ T细胞的持续增殖形成对比。

Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with systemic lupus erythematosus.

作者信息

Honda M, Mengesha E, Albano S, Nichols W S, Wallace D J, Metzger A, Klinenberg J R, Linker-Israeli M

机构信息

Department of Medicine, Cedars-Sinai Research Institute and the University of California at Los Angeles, Los Angeles, CA 90048, USA.

出版信息

Clin Immunol. 2001 May;99(2):211-221. doi: 10.1006/clim.2001.5023.

DOI:10.1006/clim.2001.5023

PMID:11318593

Abstract

To evaluate whether the immune system of systemic lupus erythematosus (SLE) patients shows features of premature aging, we compared telomere length and proliferative potential of SLE peripheral blood mononuclear cells (PBMC) (N = 90) to those of controls (N = 64). SLE samples showed accelerated loss of telomeric DNA (P = 0.00008) and higher levels of senescent (< or =5 kb) telomeric DNA (P = 0.00003). Viability cell counts and CFSE tracking in 6-week-old cell cultures indicated that SLE PBMC (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than controls (P = 0.04). However, a CD8(+)CD28(lo) T cell subset expanded preferentially in SLE-derived bulk cultures (P = 0.0009), preserved telomeric DNA (P = 0.01 vs entire CD8+), and displayed telomerase activity [2.1 telomerase arbitrary units (TAU) vs 0.5 TAU in CD8+CD28(hi) cells and 0.3 TAU in bulk PBMC; P = 0.05]. These T cell anomalies could be due to chronic in vivo stimulation of the immune system and may contribute to the immune dysregulation found in SLE.

摘要

为了评估系统性红斑狼疮（SLE）患者的免疫系统是否表现出早衰特征，我们将SLE患者外周血单个核细胞（PBMC）（N = 90）的端粒长度和增殖潜能与对照组（N = 64）进行了比较。SLE样本显示端粒DNA加速丢失（P = 0.00008），衰老（≤5 kb）端粒DNA水平更高（P = 0.00003）。在6周龄细胞培养物中的活细胞计数和CFSE追踪表明，SLE PBMC（CD8 +和CD4 + T细胞）的有丝分裂周期比对照组少，端粒也更短（P = 0.04）。然而，CD8(+)CD28(lo) T细胞亚群在SLE来源的大量培养物中优先扩增（P = 0.0009），保留了端粒DNA（与整个CD8 +相比，P = 0.01），并显示出端粒酶活性[2.1端粒酶任意单位（TAU），而CD8 + CD28(hi)细胞中为0.5 TAU，大量PBMC中为0.3 TAU；P = 0.05]。这些T细胞异常可能是由于免疫系统在体内受到慢性刺激，可能导致SLE中发现的免疫失调。