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Tumor Necrosis Factor Receptor 1 Mediates Dendritic Cell Maturation and CD8 T Cell Response through Two Distinct Mechanisms

Author(s)
Ding, Xilai; Yang, Wei; Shi, Xiaodong; Du, Peishuang; Su, Lishan; Qin, Zhihai; Chen, Jianzhu; Deng, Hongyu; ... Show more Show less
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Alternative title
TNF Receptor 1 Mediates Dendritic Cell Maturation and CD8 T Cell Response through Two Distinct Mechanisms
Terms of use
Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/
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Abstract
TNF-α and its two receptors (TNFR1 and 2) are known to stimulate dendritic cell (DC) maturation and T cell response. However, the specific receptor and mechanisms involved in vivo are still controversial. In this study, we show that in response to an attenuated mouse hepatitis virus infection, DCs fail to mobilize and up-regulate CD40, CD80, CD86, and MHC class I in TNFR1−/− mice as compared with the wild-type and TNFR2−/− mice. Correspondingly, virus-specific CD8 T cell response was dramatically diminished in TNFR1−/− mice. Adoptive transfer of TNFR1-expressing DCs into TNFR1−/− mice rescues CD8 T cell response. Interestingly, adoptive transfer of TNFR1-expressing naive T cells also restores DC mobilization and maturation and endogenous CD8 T cell response. These results show that TNFR1, not TNFR2, mediates TNF-α stimulation of DC maturation and T cell response to mouse hepatitis virus in vivo. They also suggest two mechanisms by which TNFR1 mediates TNF-α–driven DC maturation, as follows: a direct effect through TNFR1 expressed on immature DCs and an indirect effect through TNFR1 expressed on naive T cells.
Date issued
2011-06
URI
http://hdl.handle.net/1721.1/72609
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Journal of Immunology
Publisher
The American Association of Immunologists
Citation
Ding, X. et al. “TNF Receptor 1 Mediates Dendritic Cell Maturation and CD8 T Cell Response Through Two Distinct Mechanisms.” The Journal of Immunology 187.3 (2011): 1184–1191.
Version: Author's final manuscript
ISSN
0022-1767
1550-6606

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