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International Immunology Advance Access originally published online on October 26, 2006
International Immunology 2006 18(12):1771-1777; doi:10.1093/intimm/dxl111
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Distinctive role of donor strain immature dendritic cells in the creation of allograft tolerance

Yon Su Kim1, Seung Hee Yang1, Hee Gyung Kang2, Eun Young Seong1, Se Han Lee1, Wenda Gao2, James Kenny2, Xin Xiao Zheng2 and Terry B. Strom2

1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
2 Department of Medicine and Surgery, Division of Immunology and Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Correspondence to: Y. S. Kim; E-mail: yonsukim{at}snu.ac.kr

Dendritic cells (DCs) 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, we have studied the effects of immunization with allogeneic CD4+CD8–CD11c+ dendritic cell (CD4+DC) and CD4–CD8+CD11c+ dendritic cell (CD8+DC) on the allograft response. Although both immature CD4+DC and CD8+DC subsets from DBA/2 were able to prime naive allogeneic C57BL/6 (B6) T cells in mixed lymphocyte reaction (MLR), CD8+DC exerted more vigorous alloimmune responses than CD4+DC did. Also, CD4+DC-driven allogeneic T cell response was attenuated more significantly by anti-CD154 mAb than CD8+DC-driven response. Consistent with the MLR results, combined pre-treatment with CD4+DC, but not CD8+DC, plus anti-CD154 mAb produced donor strain-specific long-term graft survival and induced tolerance while treatment with CD8+DC plus anti-CD154 mAb created minimal prolongation of allograft survival in a pancreas islet transplant model (DBA/2->B6). The beneficial effects exerted by CD4+DC and anti-CD154 mAb pre-treatment were correlated with Th1 to Th2 immune deviation and with the amplified donor-specific suppressive capacity by recipient CD4+CD25+ T cells. These findings highlight the capacity of CD4+DC to modulate alloimmune responses, and suggest therapeutic approaches for the induction of donor-specific tolerance.

Keywords: dendritic cells, tolerance, transplantation

Transmitting editor: K. Inaba


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