Distinctive role of donor strain immature dendritic cells in the creation of allograft tolerance.
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.
Kim
Yon Su
YS
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yonsukim@snu.ac.kr
Yang
Seung Hee
SH
Kang
Hee Gyung
HG
Seong
Eun Young
EY
Lee
Se Han
SH
Gao
Wenda
W
Kenny
James
J
Zheng
Xin Xiao
XX
Strom
Terry B
TB
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000637:transplantation; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity; D014019:Tissue Donors / Q000145:classification; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D039521:CD11c Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens