authors contributed equally to this work.
Donor Antigen-Loaded IKK2dn Gene-Modified Dendritic Cells Prolong Allograft Survival
Article first published online: 9 FEB 2010
© 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd
Scandinavian Journal of Immunology
Volume 71, Issue 5, pages 336–344, May 2010
How to Cite
Ouyang, J., Fan, C., Wen, D., Hou, J., Du, Y., Wang, Y. and Shi, G. (2010), Donor Antigen-Loaded IKK2dn Gene-Modified Dendritic Cells Prolong Allograft Survival. Scandinavian Journal of Immunology, 71: 336–344. doi: 10.1111/j.1365-3083.2010.02384.x
- Issue published online: 14 APR 2010
- Article first published online: 9 FEB 2010
- Received 31 October 2009; Accepted 29 January 2010
Dendritic cells (DC) are key factors in regulating immune responses, and they induce immune response or tolerance depends on its maturation states. Previous studies demonstrated that blocking IKK2 in bone marrow-derived dendritic cells (BMDC) by adenoviral transfection with a kinase-defective dominant negative form of IKK2 (IKK2dn) could inhibit NF-κB activation and impair DC maturation. Here, we transfected IKK2dn into recipient rat (Lewis) BMDC by adenovirus vector (Adv-IKK2dn-DC) and found that Adv-IKK2dn-DC had reduced B7-2 and B7-1 expression under alloantigen stimulation. Their ability to induce allogeneic T-cell proliferation was markedly reduced in comparison with uninfected DC. A higher IL-10 secretion and a lower IFN-γ secretion were detected in Adv-IKK2dn-DC-stimulated allogenic T cells. Furthermore, we showed that Adv-IKK2dn-DC pulsed with BN (Brown Norway rats) splenocyte lysates markedly prolonged the survival of renal allografts in an antigen-specific manner. These findings suggested that Adv-IKK2dn-DC loaded with BN antigen could suppress anti-alloimmune response and induce tolerance to allografts, which provided an experimental base for immune tolerance induction by recipient DC loaded with donor antigens. Our finding may provide a more feasible strategy for deceased-donor renal transplantation.