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International Immunology Advance Access published online on October 26, 2006
International Immunology, 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
Received April 12, 2006
Accepted September 22, 2006

Article

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

Yon Su Kim 1 *, Seung Hee Yang 1, Hee Gyung Kang 2, Eun Young Seong 1, Se Han Lee 1, Wenda Gao 2, James Kenny 2, Xin Xiao Zheng 2, and Terry B. Strom 2

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

* To whom correspondence should be addressed.
Yon Su Kim, E-mail: yonsukim{at}snu.ac.kr


  Abstract

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.
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