Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques.
Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques.
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DOI：
10.4049/jimmunol.1100560
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发表时间：
2011-08-15
期刊：
影响因子：
--
通讯作者：
Picker LJ
中科院分区：
文献类型：
--
作者：
Cicin-Sain L;Sylwester AW;Hagen SI;Siess DC;Currier N;Legasse AW;Fischer MB;Koudelka CW;Axthelm MK;Nikolich-Zugich J;Picker LJ
尽管巨细胞病毒 (CMV) 感染在免疫功能正常的人群中基本上是良性的，但与控制这种持久性病毒相关的特异性 T 细胞反应是巨大的，并且必须终生维持。这些反应可能会随着年龄的增长而增加，并与“免疫风险状况”（IRP）相关，而“免疫风险状况”与老年人的免疫反应较差和死亡率增加有关。基于这种关联，有人认为，CMV 特异性 T 细胞反应可能会随着年龄的增长而变得功能失调，从而通过其他 T 细胞群稳态破坏、CMV 复制控制减弱和/或过度慢性炎症而导致免疫衰老的发生。在这里，我们使用恒河猴 (RM) 衰老模型来探究健康成年 RM 和老年 RM 之间 CMV 特异性 T 细胞反应的数量和质量是否存在差异，从而表现出免疫衰老的特征。我们证明，成人与老年 RM 中 CD4+ 和 CD8+ CMV 特异性 T 细胞库的大小相似，并且表现出基本相同的表型和功能特征，包括显性效应记忆 (EM) 表型、IFN-γ、TNF-α 和 IL-2 产生和细胞毒性脱颗粒的相同模式，以及最佳表位特异性 CD8+ T 细胞的类似功能亲和力。最重要的是，成人和老年 RM 对体内 CMV 攻击的反应和保护是相同的。这些数据表明，CMV 特异性 T 细胞免疫在老年 RM 中得到良好维持，并反驳了这些反应进行性功能障碍在免疫衰老发展中的主要作用。
Although Cytomegalovirus (CMV) infection is largely benign in immunocompetent people, the specific T cell responses associated with control of this persistent virus are enormous and must be maintained for life. These responses may increase with advanced age and have been linked to an “Immune Risk Profile” (IRP) that is associated with poor immune responsiveness and increased mortality in aged individuals. Based on this association, it has been suggested that CMV-specific T cell responses might become dysfunctional with age, and thereby contribute to the development of immune senescence by homeostatic disruption of other T cell populations, diminished control of CMV replication, and/or excess chronic inflammation. Here, we use the rhesus macaque (RM) model of aging to ask whether the quantity and quality of CMV-specific T cell responses differ between healthy adult RM and elderly RM that manifest hallmarks of immune aging. We demonstrate that the size of the CD4+ and CD8+ CMV-specific T cell pools are similar in adult vs. old RM, and show essentially identical phenotypic and functional characteristics, including a dominant effector memory (EM) phenotype, identical patterns of IFN-γ, TNF-α and IL-2 production and cytotoxic degranulation, and comparable functional avidities of optimal epitope-specific CD8+ T cells. Most importantly, the response to and protection against an in vivo CMV challenge were identical in adult and aged RM. These data indicate that CMV-specific T cell immunity is well maintained in old RM, and argue against a primary role for progressive dysfunction of these responses in the development of immune senescence.
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DOI：
10.1186/1742-4933-4-9
发表时间：
2007-12-11
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Aspinall, Richard;Del Giudice, Giuseppe;Sambhara, Suryaprakash
通讯作者：
Sambhara, Suryaprakash
影响因子：
6.4
作者：
Asanuma, H;Sharp, M;Arvin, AM
通讯作者：
Arvin, AM
影响因子：
4.4
作者：
Bitmansour, AD;Waldrop, SL;Picker, LJ
通讯作者：
Picker, LJ
影响因子：
4.4
作者：
Derhovanessian, Evelyna;Maier, Andrea B.;Pawelec, Graham
通讯作者：
Pawelec, Graham
影响因子：
15.3
作者：
Casazza, Joseph P.;Betts, Michael R.;Price, David A.;Precopio, Melissa L.;Ruff, Laura E.;Brenchley, Jason M.;Hill, Brenna J.;Roederer, Mario;Douek, Daniel C.;Koup, Richard A.
通讯作者：
Koup, Richard A.