Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation-induced cell death
| Autor: | Benyue Zhang, Anthony T. Vella, Robert S. Mittler, Yuanyuan Zhang, Liguo Niu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Fas Ligand Protein T cell Immunology Epitopes T-Lymphocyte Mice Transgenic Biology CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Lymphocyte Activation Lymphocyte Depletion Interleukin 21 Mice Tumor Necrosis Factor Receptor Superfamily Member 9 medicine Immunology and Allergy Cytotoxic T cell Animals Lymphocytic choriomeningitis virus IL-2 receptor fas Receptor Antigen-presenting cell Mice Knockout Cell Death ZAP70 CD137 Cell Differentiation Dendritic Cells Natural killer T cell Adoptive Transfer Mice Inbred C57BL medicine.anatomical_structure Cancer research Female Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 184(9) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|