Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people.
Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people.
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DOI：
10.1007/s11357-012-9425-7
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Pawelec, Graham
中科院分区：
文献类型：
--
作者：
Derhovanessian, Evelyna;Maier, Andrea B.;Haehnel, Karin;Zelba, Henning;de Craen, Anton J. M.;Roelofs, Helene;Slagboom, Eline P.;Westendorp, Rudi G. J.;Pawelec, Graham
通常在老年人中观察到的naïve T细胞的低百分比被认为与主要由传染病引起的死亡率有因果关系，并被视为“免疫衰老”的标志。然而，低水平的幼稚细胞是否真的与死亡率有关，还没有在纵向研究中得到验证。在这里，我们从基于人群的前瞻性Leiden 85-plus研究中提出了外周血t细胞表型与个体8年生存率之间的相关性。与直觉相反，我们发现naïve CD8+ T细胞（表征为CD45RA+CCR7+CD27+CD28+）在基线（bbbb88年）较低的频率与较好的生存率显著相关，而晚期分化效应记忆细胞（CD45RA - CCR7 - CD27 - CD28 -）的相互积累趋势也与较好的生存率相关。这些发现表明，对先前遇到的抗原特异性记忆细胞的更好保留可能在这一特定人群中提供生存优势。考虑到巨细胞病毒（CMV）的流行及其与免疫衰老的关联，我们测试了对这种潜在病原体的记忆是否与生存有关。我们发现，对CMV主要靶分子pp65和IE1产生特异性促炎反应（TNF, IFN-γ, IL-17）的个体比具有抗炎反应（IL-10）的个体具有显著的生存优势。这些发现表明，naïve T细胞的高水平可能不一定与生存优势相关，并暗示免疫监视CMV的性质可能对剩余寿命至关重要，至少在老年人中是如此。本文的在线版本（doi:10.1007/s11357-012-9425-7）包含补充材料，仅供授权用户使用。
The low percentages of naïve T cells commonly observed in elderly people are thought to be causally associated with mortality, primarily from infectious disease, and are taken as a hallmark of “immunosenescence”. Whether low levels of naive cells actually do associate with mortality has, however, not been tested in longitudinal studies. Here, we present correlations between peripheral T-cell phenotypes and 8-year survival in individuals from the population-based prospective Leiden 85-plus Study. Counter-intuitively, we found that a lower frequency of naïve CD8+ T cells (characterized as CD45RA+CCR7+CD27+CD28+) at baseline (>88 years) correlated with significantly better survival, while there was a tendency for the reciprocal accumulation of late-differentiated effector memory cells (CD45RA−CCR7−CD27−CD28−) also to associate with better survival. These findings suggest that better retention of memory cells specific for previously encountered antigens may provide a survival advantage in this particular population. Given the prevalence of Cytomegalovirus (CMV) and its reported association with immunosenescence, we tested whether memory for this potential pathogen was relevant to survival. We found that individuals mounting an exclusively pro-inflammatory ex vivo response (TNF, IFN-γ, IL-17) to the major CMV target molecules pp65 and IE1 had a significant survival advantage over those also having anti-inflammatory responses (IL-10). These findings suggest that higher levels of naïve T cells may not necessarily be associated with a survival advantage and imply that the nature of immunosurveillance against CMV may be crucial for remaining longevity, at least in the very elderly. The online version of this article (doi:10.1007/s11357-012-9425-7) contains supplementary material, which is available to authorized users.
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