Najarro Kevin, Nguyen Huy, Chen Guobing, Xu Mai, Alcorta Sandy, Yao Xu, Zukley Linda, Metter E Jeffrey, Truong Thai, Lin Yun, Li Huifen, Oelke Mathias, Xu Xiyan, Ling Shari M, Longo Dan L, Schneck Jonathan, Leng Sean, Ferrucci Luigi, Weng Nan-ping
Laboratory of Molecular Biology and Immunology.
Translational Gerontology Branch.
J Infect Dis. 2015 Oct 15;212(8):1261-9. doi: 10.1093/infdis/jiv202. Epub 2015 Mar 31.
Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown.
We selected 22 HLA-A2-positive healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T-cell response against an influenza antigen.
B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, but M1-specific CD8(+) T cells from the long telomere group exhibited significantly greater expansion in vitro than those from the short telomere group. Finally, M1-specific CD8(+) T cells that underwent more expansions had significantly longer telomeres than cells with fewer divisions.
Telomere length is positively associated with a robust lymphocyte response, and telomere attrition may contribute to the age-associated decline of adaptive immunity.
端粒为保护染色体完整性提供关键机制,其在细胞分裂后及衰老过程中的损耗在淋巴细胞中很明显。然而,端粒缩短在与年龄相关的免疫功能衰退中的意义尚不清楚。
我们选择了22名HLA - A2阳性的健康老年人,他们的端粒长度相对较短或较长,以比较他们对流感疫苗的抗体反应以及他们对流感抗原的CD8(+) T细胞反应。
对流感疫苗有强烈抗体反应的个体的B细胞端粒明显长于抗体反应差的个体。短端粒组和长端粒组的单核细胞衍生抗原呈递细胞诱导流感M1特异性CD8(+) T细胞产生相似的扩增。接种疫苗并未增加血液中M1特异性CD8(+) T细胞的T细胞,但长端粒组的M1特异性CD8(+) T细胞在体外的扩增明显大于短端粒组。最后,经历更多扩增的M1特异性CD8(+) T细胞的端粒明显长于分裂较少的细胞。
端粒长度与强大的淋巴细胞反应呈正相关,端粒损耗可能导致与年龄相关的适应性免疫衰退。