S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Distinctive role of donor strain immature dendritic cells in the creation of allograft tolerance
- Kim, Yon Su; Yang, Seung Hee; Kang, Hee Gyung; Seong, Eun Young; Lee, Se Han; Gao, Wenda; Kenny, James; Zheng, Xin Xiao; Strom, Terry B
- Issue Date
- Oxford University Press
- Int Immunol. 2006 Dec;18(12):1771-7. Epub 2006 Oct 26.
- Animals; Antigens, CD11c/metabolism; Antigens, CD4/metabolism; Antigens, CD8/metabolism; Dendritic Cells/*cytology/transplantation; *Graft Survival/physiology; Humans; *Islets of Langerhans Transplantation; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Species Specificity; *Tissue Donors/classification; *Transplantation Tolerance; *Transplantation, Homologous
- 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 T(h)1 to T(h)2 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.
- 0953-8178 (Print)
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