Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
J Immunol. 2010 Apr 1;184(7):3417-23. doi: 10.4049/jimmunol.0903442. Epub 2010 Feb 22.
Short telomeres of circulating leukocytes are a risk factor for age-related diseases, such as atherosclerosis, but the exact mechanisms generating variations in telomere length are unknown. We hypothesized that induction of differentiated T cells during chronic CMV infection would affect T cell telomere length. To test this, we measured the amount of differentiated T cells and telomere length of lymphocytes during primary CMV infection as well as CMV-seropositive and -seronegative healthy individuals. After primary CMV infection, we observed an increase in highly differentiated cells that coincided with a steep drop in telomere length. Moreover, we found in a cohort of 159 healthy individuals that telomere shortening was more rapid in CMV-seropositive individuals and correlated with the amount of differentiated T cells in both CD4(+) T cells and CD8(+) T cells. Finally, we found that telomere length measured in blood leukocytes is correlated with lymphocyte telomere length. Thus, CMV infection induces a strong decrease in T cell telomere length, which can be explained by changes in the composition of the circulating lymphocyte pool.
循环白细胞端粒较短是与年龄相关疾病(如动脉粥样硬化)的风险因素,但导致端粒长度变化的确切机制尚不清楚。我们假设慢性 CMV 感染期间诱导分化的 T 细胞将影响 T 细胞端粒长度。为了验证这一点,我们在原发性 CMV 感染期间以及 CMV 血清阳性和阴性的健康个体中测量了分化 T 细胞的数量和淋巴细胞的端粒长度。在原发性 CMV 感染后,我们观察到高度分化的细胞增加,这与端粒长度的急剧下降同时发生。此外,我们在 159 名健康个体的队列中发现,CMV 血清阳性个体的端粒缩短速度更快,与 CD4(+) T 细胞和 CD8(+) T 细胞中分化 T 细胞的数量相关。最后,我们发现血液白细胞中的端粒长度与淋巴细胞端粒长度相关。因此,CMV 感染导致 T 细胞端粒长度明显缩短,这可以通过循环淋巴细胞池组成的变化来解释。