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...

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Bibliographic Details
Published in:Immunology 2010-04, Vol.129 (4), p.567-577
Main Authors: Kang, Hee Gyung, Lee, Jung Eun, Yang, Seung Hee, Lee, Se Han, Gao, Wenda, Strom, Terry B, Oh, Keunhee, Lee, Dong-Sup, Kim, Yon Su
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells - immunology
Cell Proliferation
clonal hyporeactivity
dendritic cells
Dendritic Cells - immunology
Female
Formaldehyde - chemistry
Graft Survival - immunology
H-2 Antigens - immunology
Isoantigens - immunology
long-term graft survival
maturation
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Original
Phenotype
T-Lymphocytes, Regulatory - immunology
Tissue Donors
Tissue Fixation
tolerance
Transplantation Tolerance
Transplantation, Homologous - immunology
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Summary: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.
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2009.03158.x