Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation-induced cell death
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 184 (2010-03-31), Heft 9
Online
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Zugriff:
Agonistic anti-CD137 mAbs either positively or negatively regulate T cell function. When administered at the beginning of lymphocytic choriomeningitis virus Armstrong infection anti-CD137 induced immunosuppression and T cell deletion, and in the case of influenza infection led to increased mortality. In contrast, 72 h delay in anti-CD137 treatment led to an enhanced virus-specific CD8 T cell response and rapid viral clearance. Virus-specific CD8 T cells in anti-CD137–injected mice rapidly upregulate Fas expression, and although necessary, was insufficient to induce CD8 T cell deletion. Strikingly, CD137 signaling in T cells was found to be insufficient to induce suppression or deletion. Rather, immunosuppression and T cell deletion was only observed if CD137 signals were provided to T cells and dendritic cells (DCs). In vitro CD137 crosslinking in DCs led to phosphorylation of Stat3, and importantly, anti-CD137 treatment of lymphocytic choriomeningitis virus Armstrong infected Stat3 conditional knock-out mice induced neither immune suppression or T cell deletion. Taken together, these data suggest that CD137 signaling in DCs can regulate CD8 T cell survival through a Stat3 and Fas-mediated pathway.
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Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation-induced cell death
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Autor/in / Beteiligte Person: | Zhang, Benyue ; Vella, Anthony T. ; Mittler, Robert S. ; Zhang, Yuanyuan ; Niu, Liguo |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 184 (2010-03-31), Heft 9 |
Veröffentlichung: | 2010 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) |
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