Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation.
Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation.
复制标题
DOI：
10.4049/jimmunol.181.3.1835
复制
发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Chougnet C
中科院分区：
文献类型：
--
作者：
Lages CS;Suffia I;Velilla PA;Huang B;Warshaw G;Hildeman DA;Belkaid Y;Chougnet C
免疫功能的下降在老年人中得到了充分的描述，并且被认为是导致该人群疾病负担的重要因素。调节性 T 细胞 (Treg) 是一种 CD4+ T 细胞亚群，通常以高 CD25 表达为特征，控制啮齿动物和人类的免疫反应强度。然而，由于 CD25 表达并不能定义所有 Tregs，尤其是在老年宿主中，因此我们通过 FOXP3 的表达来表征 Tregs，FOXP3 是对 Treg 分化和功能至关重要的转录因子。老年人血液和老年小鼠淋巴组织中FOXP3+CD4+Tregs的比例增加。来自衰老宿主的 FOXP3+ Tregs 上的功能标记（如 CTLA-4 和 GITR）的表达要么保留，要么增加，具体取决于分析的组织。体外去除老年人外周Treg细胞可改善大多数受试者的效应T细胞反应。重要的是，来自年老 FoxP3-GFP 敲入小鼠的 Tregs 具有抑制性，与年轻的 Tregs 相比，每个细胞表现出更高水平的抑制。老年小鼠中Tregs比例的增加与老年小鼠慢性利什曼原虫主要感染的自发重新激活有关，这可能是因为老年Tregs有效地抑制了效应T细胞产生IFN-γ。最后，老年小鼠体内 Tregs 的消耗减轻了疾病的严重程度。因此，衰老宿主中功能性调节性T细胞的积累可能在衰老过程中慢性感染的频繁重新激活中发挥重要作用。可以设想通过控制 Treg 数量和/或活性来加强对这一脆弱人群中传染病的控制。
Declines in immune function are well described in the elderly, and are considered to contribute significantly to disease burden in this population. Regulatory T cells (Tregs), a CD4+ T cell subset usually characterized by high CD25 expression, control the intensity of immune responses, both in rodents and humans. However, because CD25 expression does not define all Tregs, especially in aged hosts, we characterized Tregs by expression of FOXP3, a transcription factor crucial for Treg differentiation and function. The proportion of FOXP3+CD4+ Tregs increased in the blood of the elderly and the lymphoid tissues of aged mice. The expression of functional markers, such as CTLA-4 and GITR, was either preserved or increased on FOXP3+ Tregs from aged hosts, depending on the tissue analyzed. In vitro depletion of peripheral Tregs from elderly humans improves effector T cell responses in most subjects. Importantly, Tregs from old FoxP3-GFP knock-in mice were suppressive, exhibiting a higher level of suppression per cell than young Tregs. The increased proportion of Tregs in aged mice was associated with the spontaneous reactivation of chronic Leishmania major infection in old mice, likely because old Tregs efficiently suppressed the production of IFN-gamma by effector T cells. Finally, in vivo depletion of Tregs in old mice attenuated disease severity. Accumulation of functional Tregs in aged hosts could therefore play an important role in the frequent reactivation of chronic infections that occurs in aging. Manipulation of Treg numbers and/or activity may be envisioned to enhance control of infectious diseases in this fragile population.
登录
查看更多内容
DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
影响因子：
12.8
作者：
Gottenberg, JE;Lavie, F;Mariette, X
通讯作者：
Mariette, X
影响因子：
4.4
作者：
Gondek, DC;Lu, LF;Noelle, RJ
通讯作者：
Noelle, RJ
影响因子：
6.4
作者：
Duggleby, Richard C.;Shaw, Tovah N. F.;Gaston, J. S. Hill
通讯作者：
Gaston, J. S. Hill
影响因子：
64.8
作者：
Belkaid, Y;Piccirillo, CA;Sacks, DL
通讯作者：
Sacks, DL