Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen.
Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen.
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DOI：
10.4049/jimmunol.181.11.7977
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发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Khan IA
中科院分区：
文献类型：
--
作者：
Moretto MM;Lawlor EM;Khan IA
Down-regulation of immune response in aging individuals puts this population at a potential risk against infectious agents. In-depth studies conducted in humans and mouse models have demonstrated that with increasing age, T cell immune response against pathogens is compromised and response to vaccinations is subdued. In the present study, using a mouse model, we demonstrate that older animals exhibit greater susceptibility to Encephalitozoon cuniculi infection, and their ability to evoke an antigen-specific T cell response at the gut mucosal site is reduced. The dampening of T cell immunity was due to the defective priming by the dendritic cells (DC) isolated from the mucosal tissues of aging animals. When primed with DC from younger mice, T cells from older animals were able to exhibit optimal antigen-specific response. The functional defect in DC from older mice can be attributed to large extent to reduced IL-15 message in these cells, which can be reversed by addition of exogenous IL-15 to the cultures. IL-15 treatment led to optimal expression of co-stimulatory molecules (CD80 and CD86) on the surface of older DC and restored their ability to prime a T cell response against the pathogen. To our knowledge, this is the first report, which demonstrates the inability of DC population from aging animals to prime a robust T cell response against an infectious agent. Moreover, the observation that IL-15 treatment can reverse this defect has far reaching implications in developing strategies to increase vaccination protocols for aging population.
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影响因子：
30.5
作者：
Kuwajima, Seiichi;Sato, Taku;Ohteki, Toshiaki
通讯作者：
Ohteki, Toshiaki
影响因子：
4.4
作者：
Miller, JP;Allman, D
通讯作者：
Allman, D
DOI：
10.1084/jem.184.5.1891
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Linton PJ;Haynes L;Klinman NR;Swain SL
通讯作者：
Swain SL
DOI：
10.1073/pnas.0506180103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Combe, CL;Moretto, MM;Khan, IA
通讯作者：
Khan, IA
影响因子：
5.3
作者：
Maletto, BA;Gruppi, A;PistoresiPalencia, MC
通讯作者：
PistoresiPalencia, MC