Human immunosenescence:: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space
Human immunosenescence:: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space
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DOI：
10.1016/s0264-410x(99)00513-7
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发表时间：
2000-02-25
期刊：
影响因子：
5.5
通讯作者：
Valensin, S
中科院分区：
文献类型：
--
作者：
Franceschi, C;Bonafè, M;Valensin, S
根据我们几年前提出的衰老重塑理论，目前关于人类免疫衰老的数据描述了一个复杂的场景，即克隆型免疫功能恶化，而祖先的先天/自然免疫功能随着年龄的增长在很大程度上保持甚至上调。从进化的角度来看，抗原是持续的终身抗原应激的原因，负责效应CD8+/CD28- T细胞的积累，幼稚T细胞（CD95-）的减少和T细胞库随着年龄的增长而显著萎缩。同时，与克隆型免疫相比，NK细胞毒性、趋化性、吞噬和补体活性不受影响或可忽略不计。因此，免疫衰老不是一种随机的退化现象，而似乎相反地概括了一种进化模式。总的来说，免疫衰老可以设想为不可避免地持续暴露于各种潜在抗原（病毒、细菌，但也包括食物和自身分子等）的结果。从这个角度来看，抗原只不过是一种特定类型的应激源，免疫衰老似乎是为免疫记忆付出的代价，即最新和最复杂的免疫类型的主要特征之一。再加上与年龄相关的胸腺退化，以及随之而来的与年龄相关的胸腺新T细胞输出减少，这种情况使身体实际上缺乏原始T细胞，因此更容易发生各种传染性和非传染性疾病。(C) 2000 Elsevier Science Ltd.版权所有。
According to the remodeling theory of aging we proposed several years ago, the current data on human immunosenescence depicts a complex scenario where clonotypical immunity deteriorates, while ancestral innate/natural immunity is largely conserved or even up-regulated with age. Under an evolutionary perspective, antigens are the cause of a persistent life-long antigenic stress, responsible for the accumulation of effector CD8+/CD28- T cells, the decrease of naive T cells (CD95-) and the marked shrinkage of T cell repertoire with age. Concomitantly, NK cytotoxicity, chemotaxis, phagocytosis and complement activities remain unaffected or negligibly affected, in comparison to clonotypical immunity. Thus, immunosenescence is not a random deteriorative phenomenon but appears to inversely recapitulate an evolutionary pattern. On the whole, immunosenescence can be envisaged as the result of the continuous challenge of the unavoidable exposure to a variety of potential antigens (viruses, bacteria, but also food and self molecules among others). From this perspective antigens are nothing else than a particular type of stressor and immunosenescence appears to be the price paid to immunological memory, i.e. one of the main characteristics of the most evolutionary recent and sophisticated type of immunity. Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of new T cells, this situation leaves the body practically devoid of virgin T cells, and thus likely more prone to a variety of infectious and non infectious diseases. (C) 2000 Elsevier Science Ltd. All rights reserved.