Korean J Nephrol.  2006 Mar;25(2):195-204.

The Differential Effects of Donor-Strain Immature Dendritic Cell Subtypes and the Blockade of CD40/CD154 Pathway on the Creation of Allograft Tolerance

• Yang SH
• Seong EY
• Lee JE
• Shin JH
• Zhe JJ
• Sangidorj
• Kim YS

Abstract

BACKGOUND: Dendritic cells (DC) are pivotal antigen presenting cells and serve a unique role in initiating immunity. To test the hypothesis that pre-immunization of recipient with certain DC subsets of donor origin can influence graft outcome.
METHODS
We have studied the effects of immunization with allogeneic CD4+CD11c+(MDC) and CD8+CD11c+(LDC) DCs on the allograft response.
RESULTS
Both immature MDC and LDC subsets from DBA/2 were able to prime naive allogeneic C57BL/6 (B6) T cells in MLR. In vitro allogeneic T cell responses were attenuated by the addition of anti-CD154 mAb into the culture. T cells from B6 mice that received DBA/2 MDC intravenously 4 weeks before testing mounted weaker MLR driven cell proliferation than T cells from LDC pretreated B6 mice. Consistent with the MLR results, combined pretreatment with MDC, but not LDC, plus anti-CD154 mAb produced donor-strain specific long-term graft survival and induced tolerance while treatment with LDC plus anti-CD154 mAb created minimal prolongation of allograft survival in a pancreas islet transplant model (DBA/2->B6). The beneficial effects exerted by MDC and anti-CD154 mAb pretreatment were correlated with TH1 to TH2 immune deviation and with the amplified donor-specific suppressive capacity by recipient CD4+CD25+T cells.
CONCLUSION
These findings highlight the capacity of MDC to modulate alloimmune responses, and suggest therapeutic approaches for the induction of donor specific tolerance.

Keyword

Dendritic cell subtypes; Co-stimulation blockade; Donor specific tolerance

MeSH Terms

Allografts*
Animals
Antigen-Presenting Cells
Cell Proliferation
Dendritic Cells*
Graft Survival
Humans
Immunization
Mice
Pancreas
T-Lymphocytes
Tissue Donors
Transplantation Tolerance*
Transplants