Ouyang Qin, Wagner Wolfgang M, Zheng Wei, Wikby Anders, Remarque Ed J, Pawelec Graham
Tübingen Ageing and Tumour Immunology Group, Section for Transplantation Immunology and Immunohematology, University of Tübingen, Tübingen, Germany.
Exp Gerontol. 2004 Apr;39(4):607-13. doi: 10.1016/j.exger.2003.11.016.
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.
携带巨细胞病毒（CMV）单表位受体的外周CD8(+) T细胞大量克隆扩增在老年人中很常见，且可能与预测死亡率的免疫风险表型相关。为了研究衰老对CMV特异性CD8(+) T细胞产生1型和2型细胞因子能力的影响，我们检测了CMV血清阳性的老年和年轻供体在CMV肽抗原存在时产生干扰素-γ和白细胞介素-10的CD8(+) T细胞反应。我们发现，老年人中A2/NLV特异性CD8(+) T淋巴细胞的大量扩增伴随着抗原反应性的部分丧失，这表现为产生抗原特异性干扰素-γ和白细胞介素-10的细胞频率大幅下降。因此，尽管携带特异性抗原受体，但根据这些标准，老年人中大多数克隆扩增的CMV特异性CD8(+)细胞功能失调。我们的数据表明老年人倾向于产生更具抗炎性的反应。功能失调的CMV特异性细胞的积累可能会占据“免疫空间”，并减少可用于识别新抗原的T细胞库。这可能解释了老年人中许多传染病发病率增加的原因。
