Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
International Immunology
Year: 2009  |  Volume: 21  |  Issue: 10  |  Page No.: 1135 - 1144

A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse signaling

S Ju, Y Ge, H Qiu, B Lu, Y Qiu, J Fu, G Liu, Q Wang, Y Hu, Y Shu and X. Zhang    

Abstract:

Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs (DCs-4-1BBL) not only express higher levels of CD86, CD83 and HLA-DR, when compared with the Mo-DCs matured by tumor necrosis factor , but also exhibit a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, M-CSF and Flt3 ligand (FL) were found in the anti-4-1BBL-differentiation culture. Neutralizing M-CSF, GM-CSF and FL inhibited Mo-DC proliferation stimulated by anti-4-1BBL mAb, suggesting that M-CSF, GM-CSF and FL are involved in cell proliferation stimulated by anti-4-1BBL. Further analysis of the DCs-4-1BBL showed increased secretion of Th1-type cytokines IL-12 and IFN- and decreased secretion of IL-10. DCs-4-1BBL induced much stronger proliferative responses in the mixed lymphocyte reaction assay when compared with DCs derived by GM-CSF. Moreover, DCs-4-1BBL preferentially induced Th1 responses. We have further demonstrated that anti-4-1BBL antibody stimulated nuclear translocation of NF-B from the cytoplasm in monocytes, suggesting that reverse signaling by 4-1BBL is likely responsible for mediating DC differentiation. Collectively, we have found that reverse signaling of 4-1BBL promotes the differentiation of potent Th1-inducing DCs from human monocytes.

View Fulltext    |   Related Articles   |   Back
   
 
 
 
  Related Articles

No Article Found
 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility