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Prevention of Acute and Chronic Allograft Rejection by Combinations of Tolerogenic Dendritic Cells

Huang, Y. L.; Wang, Y. Z.; Chen, J. B.; Wang, F.; Kang, X. P.; Xia, J. J.; Lan, T. S.; Xie, B. Y.; Ekberg, Henrik LU and Wang, X. M., et al. (2011) In Scandinavian Journal of Immunology 73(2). p.91-101
Abstract
It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL-12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion. Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor-derived MMC-DC prolonged the... (More)
It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL-12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion. Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor-derived MMC-DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c x C57BL/6) derived MMC-DC were injected together with anti-CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1-derived tolerogenic DC have a synergistic effect on induction and maintenance of T-cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice. (Less)
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Scandinavian Journal of Immunology
volume
73
issue
2
pages
91 - 101
publisher
Wiley-Blackwell
external identifiers
  • wos:000285875800003
  • scopus:78650775606
ISSN
1365-3083
DOI
10.1111/j.1365-3083.2010.02485.x
language
English
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yes
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54cecc7f-fcb5-465b-84a7-19297563e9af (old id 1790993)
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2011-03-02 14:44:28
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@article{54cecc7f-fcb5-465b-84a7-19297563e9af,
  abstract     = {It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL-12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion. Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor-derived MMC-DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c x C57BL/6) derived MMC-DC were injected together with anti-CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1-derived tolerogenic DC have a synergistic effect on induction and maintenance of T-cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice.},
  author       = {Huang, Y. L. and Wang, Y. Z. and Chen, J. B. and Wang, F. and Kang, X. P. and Xia, J. J. and Lan, T. S. and Xie, B. Y. and Ekberg, Henrik and Wang, X. M. and Qi, Z. Q.},
  issn         = {1365-3083},
  language     = {eng},
  number       = {2},
  pages        = {91--101},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Prevention of Acute and Chronic Allograft Rejection by Combinations of Tolerogenic Dendritic Cells},
  url          = {http://dx.doi.org/10.1111/j.1365-3083.2010.02485.x},
  volume       = {73},
  year         = {2011},
}