PDF(Pubmed)
Abstract：
T cells have been shown to maintain a lower percentage (heteroplasmy) of the pathogenic m.3243A>G variant (MT-TL1, associated with maternally inherited diabetes and deafness [MIDD] and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS]). The mechanism(s) underlying this purifying selection, however, remain unknown. Here we report that purified patient memory CD4+ T cells have lower bulk m.3243A>G heteroplasmy compared to naïve CD4+ T cells. In vitro activation of naïve CD4+ m.3243A>G patient T cells results in lower bulk m.3243A>G heteroplasmy after proliferation. Finally, m.3243A>G patient T cell receptor repertoire sequencing reveals relative oligoclonality compared to controls. These data support a role for T cell activation in peripheral, purifying selection against high m.3243A>G heteroplasmy T cells at the level of the cell, in a likely cell-autonomous fashion.
摘要：
已显示T细胞维持致病性m.3243A>G变体（MT-TL1，与母体遗传性糖尿病和耳聋[MIDD]和线粒体脑肌病伴乳酸性酸中毒和中风样发作[MELAS]相关）的较低百分比（异质）。这种纯化选择的潜在机制，然而,仍然未知。在这里，我们报告，纯化的患者记忆CD4+T细胞具有较低的体积m.3243A>G异质体相比，幼稚CD4+T细胞。原始CD4+m.3243A>G患者T细胞的体外活化在增殖后导致较低的体积m.3243A>G异质体。最后,m.3243A>G患者T细胞受体库测序揭示了与对照相比的相对寡克隆性。这些数据支持外周T细胞活化的作用，在细胞水平上针对高m.3243A>G异质T细胞的纯化选择，以一种可能的细胞自主方式。
