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Arsenic trioxide is a novel agent for combination therapy to prolong heart allograft survival in allo-primed T cells transferred mice

Lin, Yingying; Dai, Helong; Su, Jingjun; Yan, Guoliang; Xi, Yanfeng; Ekberg, Henrik LU ; Chen, Jibing and Qi, Zhongquan (2011) In Transplant Immunology 25(4). p.194-201
Abstract
Alloreactive memory T cells are major barriers to transplantation acceptance due to their capacity to accelerate rejection. Here, we investigated the effects of combined treatment with arsenic trioxide (As(2)O(3)) and blocking monoclonal antibodies (mAb) against CD154 and LFA-1 (anti-CD154/LFA-1) on graft survival as well as changes in pathology and immunological responses in mice with adoptively transferred allo-primed T cells. The mean survival time (MST) for the cardiac allografts in recipient mice receiving the combination of As(2)O(3) and anti-CD154/LFA-1 was significantly longer (>113.7 days) compared to those receiving anti-CD154/LFA-1 (232 days), As(2)O(3) (12.5 days) alone or no treatment (5.5 days). This combined strategy... (More)
Alloreactive memory T cells are major barriers to transplantation acceptance due to their capacity to accelerate rejection. Here, we investigated the effects of combined treatment with arsenic trioxide (As(2)O(3)) and blocking monoclonal antibodies (mAb) against CD154 and LFA-1 (anti-CD154/LFA-1) on graft survival as well as changes in pathology and immunological responses in mice with adoptively transferred allo-primed T cells. The mean survival time (MST) for the cardiac allografts in recipient mice receiving the combination of As(2)O(3) and anti-CD154/LFA-1 was significantly longer (>113.7 days) compared to those receiving anti-CD154/LFA-1 (232 days), As(2)O(3) (12.5 days) alone or no treatment (5.5 days). This combined strategy distinctly inhibited lymphocyte infiltration in grafts, proliferation of splenic T cells and the generation of memory T cells in spleens. Moreover, the combined treatment caused the significant down-regulation of IL-2 and IFN-gamma accompanied by increased expression of TGF-beta and regulatory T cells (Tregs) in spleens, which led to long-term cardiac allograft survival in recipient mice. These results highlight the potential application of As(2)O(3) and its contribution in combination therapy with antibody blockade to delay rejection by memory T cells. (C) 2011 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arsenic trioxide, Cardiac transplantation, Memory T cells
in
Transplant Immunology
volume
25
issue
4
pages
194 - 201
publisher
Elsevier
external identifiers
  • wos:000298908900004
  • scopus:80054076092
ISSN
1878-5492
DOI
10.1016/j.trim.2011.08.002
language
English
LU publication?
yes
id
cc1b16b6-22f7-45f5-aaca-196a52c9d7f9 (old id 2348513)
date added to LUP
2012-03-01 11:21:22
date last changed
2017-09-17 04:01:22
@article{cc1b16b6-22f7-45f5-aaca-196a52c9d7f9,
  abstract     = {Alloreactive memory T cells are major barriers to transplantation acceptance due to their capacity to accelerate rejection. Here, we investigated the effects of combined treatment with arsenic trioxide (As(2)O(3)) and blocking monoclonal antibodies (mAb) against CD154 and LFA-1 (anti-CD154/LFA-1) on graft survival as well as changes in pathology and immunological responses in mice with adoptively transferred allo-primed T cells. The mean survival time (MST) for the cardiac allografts in recipient mice receiving the combination of As(2)O(3) and anti-CD154/LFA-1 was significantly longer (>113.7 days) compared to those receiving anti-CD154/LFA-1 (232 days), As(2)O(3) (12.5 days) alone or no treatment (5.5 days). This combined strategy distinctly inhibited lymphocyte infiltration in grafts, proliferation of splenic T cells and the generation of memory T cells in spleens. Moreover, the combined treatment caused the significant down-regulation of IL-2 and IFN-gamma accompanied by increased expression of TGF-beta and regulatory T cells (Tregs) in spleens, which led to long-term cardiac allograft survival in recipient mice. These results highlight the potential application of As(2)O(3) and its contribution in combination therapy with antibody blockade to delay rejection by memory T cells. (C) 2011 Elsevier B.V. All rights reserved.},
  author       = {Lin, Yingying and Dai, Helong and Su, Jingjun and Yan, Guoliang and Xi, Yanfeng and Ekberg, Henrik and Chen, Jibing and Qi, Zhongquan},
  issn         = {1878-5492},
  keyword      = {Arsenic trioxide,Cardiac transplantation,Memory T cells},
  language     = {eng},
  number       = {4},
  pages        = {194--201},
  publisher    = {Elsevier},
  series       = {Transplant Immunology},
  title        = {Arsenic trioxide is a novel agent for combination therapy to prolong heart allograft survival in allo-primed T cells transferred mice},
  url          = {http://dx.doi.org/10.1016/j.trim.2011.08.002},
  volume       = {25},
  year         = {2011},
}