Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens.
The maturation of antigen-presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre-treating recipients with bone-marrow-derived donor-strain fixed immature DCs (FIDCs). Donor-strain-derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T-cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T-cell response. T cells that had previously been exposed to FIDCs maintained naïve phenotypes and were unable to extensively divide after injection into lethally irradiated donor-strain mice. The pre-treatment of recipients with donor-strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T-cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4(+) CD25(+) T cells. Consequently, FIDC-induced T-cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long-term graft survival.
Kang
Hee Gyung
HG
Kidney Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Lee
Jung Eun
JE
Yang
Seung Hee
SH
Lee
Se Han
SH
Gao
Wenda
W
Strom
Terry B
TB
Oh
Keunhee
K
Lee
Dong-Sup
DS
Kim
Yon Su
YS
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005557:Formaldehyde / Q000737:chemistry; D006085:Graft Survival / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors; D016707:Tissue Fixation; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous / Q000276:immunology
D006183:H-2 Antigens; D007519:Isoantigens; D005557:Formaldehyde