| First Author | Zhang B | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 9 | Pages | 4770-8 |
| PubMed ID | 20351189 | Mgi Jnum | J:160463 |
| Mgi Id | MGI:4454492 | Doi | 10.4049/jimmunol.0902713 |
| Citation | Zhang B, et al. (2010) Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation-induced cell death. J Immunol 184(9):4770-8 |
| abstractText | 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. |
