Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
复制标题
DOI：
10.4049/jimmunol.1203267
复制
发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Akbar AN
中科院分区：
文献类型：
--
作者：
Griffiths SJ;Riddell NE;Masters J;Libri V;Henson SM;Wertheimer A;Wallace D;Sims S;Rivino L;Larbi A;Kemeny DM;Nikolich-Zugich J;Kern F;Klenerman P;Emery VC;Akbar AN
在衰老过程中调节记忆性CD 8 + T细胞功能和稳态的机制尚不清楚。再表达CD 45 RA的CD 8+效应记忆T细胞（EMRA T细胞）在老年人中显著增加，衰老和持续性巨细胞病毒（CMV）感染是该过程中的独立因素。我们使用在CD 8结合结构域中突变的MHC I类四聚体复合物来鉴定具有高抗原结合亲合力的CMV特异性CD 8 + T细胞。在HLA-A*0201的个体中，表达CD 45 RA并对pp 65蛋白（NLV表位）具有特异性的CD 8 + T细胞比表达CD 45 RO的CD 8 + T细胞具有更低的亲合力，并在特异性活化后表现出降低的细胞因子分泌和细胞溶解潜力。此外，低亲和力NLV特异性CD 8 + T细胞在老年人中显著增加。用CMV裂解物刺激血液白细胞可诱导高水平的IFNα，进而诱导IL-15产生。此外，将IL-15添加到CD 45 RA − CD 45 RO + CMV特异性CD 8 + T细胞诱导CD 45 RA表达，而抗原活化的细胞保持CD 45 RO+。这提出了以下可能性：非特异性细胞因子驱动的具有较低抗原结合亲合力的CMV特异性CD 8 + CD 45 RA + T细胞的积累可能加剧病毒再活化对衰老期间CMV感染个体中T细胞库偏斜的影响。
The mechanisms regulating memory CD8+ T cell function and homeostasis during ageing are unclear. CD8+ effector memory T cells that re-express CD45RA (EMRA T cells) increase considerably in older humans and both ageing and persistent cytomegalovirus (CMV) infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8+ T cells with high antigen binding avidity. In individuals who were HLA-A*0201, CD8+ T cells that expressed CD45RA and were specific for the pp65 protein (NLV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLV-specific CD8+ T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFNα that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA−CD45RO+ CMV-specific CD8+ T cells induced CD45RA expression while antigen activated cells remained CD45RO+. This raises the possibility that non-specific cytokine driven accumulation of CMV-specific CD8+ CD45RA+ T cells with lower antigen binding avidity may exacerbate the effects of viral re-activation on skewing the T cell repertoire in CMV infected individuals during ageing.
登录
查看更多内容
影响因子：
3.8
作者：
Castillo, Eliseo F.;Schluns, Kimberly S.
通讯作者：
Schluns, Kimberly S.
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
3.7
作者：
FELDMAN, SB;FERRARO, M;FITZGERALDBOCARSLY, P
通讯作者：
FITZGERALDBOCARSLY, P
影响因子：
4.4
作者：
Hamann, D;Kostense, S;van Lier, RAW
通讯作者：
van Lier, RAW
DOI：
10.1073/pnas.0707570104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Harari, Alexandre;Cellerai, Cristina;Pantaleo, Giuseppe
通讯作者：
Pantaleo, Giuseppe