Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV) in healthy subjects.
Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV) in healthy subjects.
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DOI：
10.1186/1742-4933-7-14
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发表时间：
2010-10-20
期刊：
影响因子：
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通讯作者：
Correale P
中科院分区：
文献类型：
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作者：
Cusi MG;Martorelli B;Di Genova G;Terrosi C;Campoccia G;Correale P
呼吸道合胞病毒(RSV)是引起婴幼儿呼吸道疾病的主要病原体，也是老年人严重疾病的重要原因，因为感染对再次感染提供了有限的免疫保护。为了解释这一现象，我们调查了不同年龄(20-40岁；41-60岁和60岁)的健康成年人在中枢和效应器记忆、RSV特异性CD8+T细胞记忆免疫反应和调节性T细胞表达状态方面是否存在差异。在这些捐献者的外周血中，我们无法检测到任何与年龄相关的中央(CD45RA-CCR7+)和效应(CD45RA-CCR7-)记忆T细胞频率的差异。相反，我们发现在老年人中免疫抑制调节性(CD4+25+FoxP3+)T细胞(Treg)显著增加。对这些捐献者的外周血单个核细胞(PBMC)进行的RSV五聚体免疫荧光分析显示，老年人表达白细胞介素7受体α(IL-7Rα)的长效RSV特异性CD8+记忆性T细胞前体细胞显著减少。这一效应与Th1(干扰素-γ和肿瘤坏死因子-α)向Th2(IL-10)功能表型的渐进性转换是平行的。相反，Treg的表达随着年龄的增长而增加。在老年供者中发现Treg过度表达状态、显著的Th2反应和低效的RSV特异性效应记忆CD8+T细胞扩增，可以解释为什么对RSV再感染的保护作用较差，以及在这一人群中患RSV相关严重疾病的风险增加。我们的发现也为新的治疗角度奠定了基础，可以限制或预防老年人严重的RSV感染。
Respiratory syncytial virus (RSV) is the major pathogen causing respiratory disease in young infants and it is an important cause of serious illness in the elderly since the infection provides limited immune protection against reinfection. In order to explain this phenomenon, we investigated whether healthy adults of different age (20-40; 41-60 and > 60 years), have differences in central and effector memory, RSV-specific CD8+ T cell memory immune response and regulatory T cell expression status. In the peripheral blood of these donors, we were unable to detect any age related difference in term of central (CD45RA-CCR7+) and effector (CD45RA-CCR7-) memory T cell frequency. On the contrary, we found a significant increase in immunosuppressive regulatory (CD4+25+FoxP3+) T cells (Treg) in the elderly. An immunocytofluorimetric RSV pentamer analysis performed on these donors' peripheral blood mononuclear cells (PBMCs), in vitro sensitized against RSV antigen, revealed a marked decline in long-lasting RSV specific CD8+ memory T cell precursors expressing interleukin 7 receptor α (IL-7Rα), in the elderly. This effect was paralleled by a progressive switch from a Th1 (IFN-γ and TNF-α) to a Th2 (IL-10) functional phenotype. On the contrary, an increase in Treg was observed with aging. The finding of Treg over-expression status, a prominent Th2 response and an inefficient RSV-specific effector memory CD8+ T cell expansion in older donors could explain the poor protection against RSV reinfection and the increased risk to develop an RSV-related severe illness in this population. Our finding also lays the basis for new therapeutic perspectives that could limit or prevent severe RSV infection in elderly.