Journal
BLOOD
Volume 115, Issue 6, Pages 1156-1165Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-07-235382
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation)
- Ministry of Science, Research
- Arts Baden-Wurttemberg
- European Social Fund (ESF)
- Deutsche Jose Carreras Leukamie-Stiftung eV
- Deutscher Akademischer Austauschdienst (DAAD
- German Academic Exchange Service)
- US Public Health Service [P50 CA97274]
Ask authors/readers for more resources
Human plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB(+) pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC-T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations. (Blood. 2010;115:1156-1165)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available