Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults.
Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults.
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DOI：
10.1111/imm.12409
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发表时间：
2015-04
期刊：
影响因子：
6.4
通讯作者：
Akbar AN
中科院分区：
文献类型：
--
作者：
Riddell NE;Griffiths SJ;Rivino L;King DC;Teo GH;Henson SM;Cantisan S;Solana R;Kemeny DM;MacAry PA;Larbi A;Akbar AN
抗原特异性多功能T细胞在激活后同时分泌干扰素-γ、白细胞介素-2和肿瘤坏死因子-α，对于控制许多感染非常重要。目前尚不清楚这些 CD8+ T 细胞是否处于分化的早期或晚期，以及端粒侵蚀是否限制了它们的复制能力。我们开发了一种多参数流式细胞术方法，用于研究单个巨细胞病毒 (CMV) 抗原特异性 CD8+ T 细胞的分化（CD45RA 和 CD27 表面表型）、功能（细胞因子产生）和复制能力（端粒长度）之间的关系。这涉及表面和细胞内细胞染色以及荧光原位杂交以检测端粒（流式 FISH）。终末期/衰老 CD8+ CD45RA+ CD27− T 细胞亚群在衰老过程中显着增加，并且在 CMV 免疫反应受试者中这一现象被夸大。然而，这些终末期细胞不具有最短的端粒，这意味着诱导其衰老的其他非端粒相关机制。在高加索人和亚洲人队列中，由 CD45RA 和 CD27 表达定义的所有四个子集中的总端粒长度和 CMV (NLV) 特异性 CD8+ T 细胞的端粒长度在老年人中均显着短于年轻人。经抗 CD3 或 NLV 肽刺激后，在两个年龄组的所有分化阶段的 CD8+ T 细胞中都发现了相似比例的三重细胞因子产生细胞。此外，与激活后仅产生一种或两种细胞因子的细胞相比，这些多功能细胞具有中等端粒长度。因此，分泌干扰素-γ、白细胞介素-2和肿瘤坏死因子-α的整体和CMV（NLV）特异性CD8+T细胞处于分化的中间阶段，并且不受端粒过度侵蚀的限制。
Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8+ T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8+ T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8+ CD45RA+ CD27− T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8+ T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8+ T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8+ T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion.
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影响因子：
3.7
作者：
Caccamo N;Guggino G;Meraviglia S;Gelsomino G;Di Carlo P;Titone L;Bocchino M;Galati D;Matarese A;Nouta J;Klein MR;Salerno A;Sanduzzi A;Dieli F;Ottenhoff TH
通讯作者：
Ottenhoff TH
影响因子：
2.5
作者：
Montpetit AJ;Alhareeri AA;Montpetit M;Starkweather AR;Elmore LW;Filler K;Mohanraj L;Burton CW;Menzies VS;Lyon DE;Jackson-Cook CK
通讯作者：
Jackson-Cook CK
影响因子：
2.2
作者：
Kapoor, Veena;Hakim, Fran T.;Telford, William G.
通讯作者：
Telford, William G.
影响因子：
6.4
作者：
Libri, Valentina;Azevedo, Rita I.;Akbar, Arne N.
通讯作者：
Akbar, Arne N.
DOI：
10.1084/jem.186.9.1407
发表时间：
1997-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hamann D;Baars PA;Rep MH;Hooibrink B;Kerkhof-Garde SR;Klein MR;van Lier RA
通讯作者：
van Lier RA