Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly
Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly
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DOI：
10.1016/j.exger.2003.11.016
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发表时间：
2004-04-01
影响因子：
3.9
通讯作者：
Pawelec, G
中科院分区：
文献类型：
--
作者：
Qin, OY;Wagner, WM;Pawelec, G
携带CMV单一表位受体的外周CD8(+)T细胞的大量克隆性扩张在老年人中很常见，可能与预测死亡率的免疫风险表型有关。为研究增龄对CMV特异性CD8(+)T细胞产生1型和2型细胞因子能力的影响，检测了CMV血清阳性的老年和青年献血者在CMV多肽存在下产生干扰素-γ和IL-10、CD8(+)T细胞的反应。我们发现，在老年人中，A2/NLV特异性CD8+T淋巴细胞的大量扩张伴随着抗原反应性的部分丧失，这反映在抗原特异性干扰素-γ和IL-10产生细胞的频率大大降低。因此，尽管携带特定的抗原受体，但根据这些标准，大多数老年人克隆扩增的CMV特异性CD8+细胞是功能障碍的。我们的数据表明，老年人倾向于更抗炎的反应。功能失调的CMV特异性细胞的积累可能会填满免疫空间，减少T细胞对新抗原的可用能力。这可能是许多传染病在老年人中发病率增加的原因。(C)2004 Elsevier Inc.保留所有权利。
Large clonal expansions of peripheral CD8(+) T cells carrying receptors for single epitopes of CMV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. To study the effect of ageing on the ability of CMV-specific CD8(+) T cells to produce type 1- and type 2-cytokines, interferon-gamma-and IL-10-producing, CD8(+) T cell responses in the presence of CMV peptide antigen were measured in CMV-seropositive old and young donors. We found that large expansions of A2/NLV-specific CD8+ T lymphocytes in the elderly are accompanied by a partial loss of antigen responsiveness as reflected in a greatly decreased frequency of antigen-specific IFN-gamma- and IL-10-producing cells. Thus, despite carrying specific antigen receptors, the majority of the clonally expanded CMV-specific CD8+ cells in the elderly was dysfunctional according to these criteria. Our data indicated a bias towards a more anti-inflammatory response in the elderly. The accumulation of dysfunctional CMV-specific cells might fill the 'immunological space' and decrease the available repertoire of T cells for novel antigens. This might account for the increased incidence of many infectious diseases in the elderly. (C) 2004 Elsevier Inc. All rights reserved.