Plasmacytoid DC from aged mice down-regulate CD8 T cell responses by inhibiting cDC maturation after Encephalitozoon cuniculi infection.
Plasmacytoid DC from aged mice down-regulate CD8 T cell responses by inhibiting cDC maturation after Encephalitozoon cuniculi infection.
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DOI：
10.1371/journal.pone.0020838
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Khan IA
中科院分区：
文献类型：
--
作者：
Gigley JP;Khan IA
Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations.
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影响因子：
30.5
作者：
Cella, M;Facchetti, F;Colonna, M
通讯作者：
Colonna, M
DOI：
10.4049/jimmunol.0900582
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castellaneta A;Sumpter TL;Chen L;Tokita D;Thomson AW
通讯作者：
Thomson AW
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：
Decman, Vilma;Laidlaw, Brian J.;Wherry, E. John
通讯作者：
Wherry, E. John
衰老过程中小鼠树突状细胞抗肿瘤功能障碍的机制。
影响因子：
5.8
作者：
Grolleau-Julius, Annabelle;Abernathy, Lisa;Harning, Erin;Yung, Raymond L.
通讯作者：
Yung, Raymond L.