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Blockade of CD27/CD70 pathway to reduce the generation of memory T cells and markedly prolong the survival of heart allografts in presensitized mice

Dai, Helong; Chen, Jibing; Shao, Wei; Wang, Feng; Xu, Shuo; Peng, Yuanzheng; Lin, Yingying; Xia, Junjie; Ekberg, Henrik LU and Wang, Xiaomin, et al. (2011) In Transplant Immunology 24(4). p.195-202
Abstract
Background: Alloreactive memory T cells are a major obstacle to transplantation acceptance due to their capacity for accelerated rejection. Methods: C57BL/6 mice that had rejected BALB/c skin grafts 4 weeks earlier were used as recipients. The recipient mice were treated with anti-CD154/LFA-1 with or without anti-CD70 during the primary skin transplantation and anti-CD154/LFA-1 or not during the secondary transplantation of BALB/c heart. We evaluated the impact of combinations of antibody-mediated blockade on the generation of memory T cells and graft survival after fully MHC-mismatched transplantations. Results: One month after the primary skin transplantation, the proportions of CD4(+) memory T cells/CD4(+) T cells and CD8(+)memory T... (More)
Background: Alloreactive memory T cells are a major obstacle to transplantation acceptance due to their capacity for accelerated rejection. Methods: C57BL/6 mice that had rejected BALB/c skin grafts 4 weeks earlier were used as recipients. The recipient mice were treated with anti-CD154/LFA-1 with or without anti-CD70 during the primary skin transplantation and anti-CD154/LFA-1 or not during the secondary transplantation of BALB/c heart. We evaluated the impact of combinations of antibody-mediated blockade on the generation of memory T cells and graft survival after fully MHC-mismatched transplantations. Results: One month after the primary skin transplantation, the proportions of CD4(+) memory T cells/CD4(+) T cells and CD8(+)memory T cells/CD8(+) T cells in the anti-CD154/LFA-1 combination group were 47.32 +/- 428% and 23.18 +/- 2.77%, respectively. In the group that included anti-CD70 treatment, the proportions were reduced to 34.10 +/- 2.71% and 12.19 +/- 3.52% (P<0.05 when comparing the proportion of memory T cells between the two groups). The addition of anti-CD70 to the treatment regimen prolonged the mean survival time following secondary heart transplantation from 10 days to more than 90 days (P<0.001). Furthermore, allogenic proliferation of recipient splenic T cells and graft-infiltrating lymphocytes were significantly decreased. Meanwhile, the proportion of regulatory T cells was increased to 9.46 +/- 1.48% on day 100 post-transplantation (P<0.05). Conclusions: The addition of anti-CD70 to the anti-CD154/LFA-1 combination given during the primary transplantation reduced the generation of memory T cells. This therapy regimen provided a potential means to alleviate the accelerated rejection mediated by memory T cells during secondary heart transplantation and markedly prolong the survival of heart allografts. (C) 2011 Elsevier B.V. All rights reserved. (Less)
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publication status
published
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keywords
Costimulatory blockade, Anti-CD70, Memory T cells, Heart transplantation
in
Transplant Immunology
volume
24
issue
4
pages
195 - 202
publisher
Elsevier
external identifiers
  • wos:000291287200001
  • scopus:79955470860
ISSN
1878-5492
DOI
10.1016/j.trim.2011.02.002
language
English
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yes
id
b6d0f522-eb97-40f5-bb91-34c542fb8560 (old id 1985122)
date added to LUP
2011-07-01 09:07:29
date last changed
2017-01-01 03:13:47
@article{b6d0f522-eb97-40f5-bb91-34c542fb8560,
  abstract     = {Background: Alloreactive memory T cells are a major obstacle to transplantation acceptance due to their capacity for accelerated rejection. Methods: C57BL/6 mice that had rejected BALB/c skin grafts 4 weeks earlier were used as recipients. The recipient mice were treated with anti-CD154/LFA-1 with or without anti-CD70 during the primary skin transplantation and anti-CD154/LFA-1 or not during the secondary transplantation of BALB/c heart. We evaluated the impact of combinations of antibody-mediated blockade on the generation of memory T cells and graft survival after fully MHC-mismatched transplantations. Results: One month after the primary skin transplantation, the proportions of CD4(+) memory T cells/CD4(+) T cells and CD8(+)memory T cells/CD8(+) T cells in the anti-CD154/LFA-1 combination group were 47.32 +/- 428% and 23.18 +/- 2.77%, respectively. In the group that included anti-CD70 treatment, the proportions were reduced to 34.10 +/- 2.71% and 12.19 +/- 3.52% (P&lt;0.05 when comparing the proportion of memory T cells between the two groups). The addition of anti-CD70 to the treatment regimen prolonged the mean survival time following secondary heart transplantation from 10 days to more than 90 days (P&lt;0.001). Furthermore, allogenic proliferation of recipient splenic T cells and graft-infiltrating lymphocytes were significantly decreased. Meanwhile, the proportion of regulatory T cells was increased to 9.46 +/- 1.48% on day 100 post-transplantation (P&lt;0.05). Conclusions: The addition of anti-CD70 to the anti-CD154/LFA-1 combination given during the primary transplantation reduced the generation of memory T cells. This therapy regimen provided a potential means to alleviate the accelerated rejection mediated by memory T cells during secondary heart transplantation and markedly prolong the survival of heart allografts. (C) 2011 Elsevier B.V. All rights reserved.},
  author       = {Dai, Helong and Chen, Jibing and Shao, Wei and Wang, Feng and Xu, Shuo and Peng, Yuanzheng and Lin, Yingying and Xia, Junjie and Ekberg, Henrik and Wang, Xiaomin and Qi, Zhongquan},
  issn         = {1878-5492},
  keyword      = {Costimulatory blockade,Anti-CD70,Memory T cells,Heart transplantation},
  language     = {eng},
  number       = {4},
  pages        = {195--202},
  publisher    = {Elsevier},
  series       = {Transplant Immunology},
  title        = {Blockade of CD27/CD70 pathway to reduce the generation of memory T cells and markedly prolong the survival of heart allografts in presensitized mice},
  url          = {http://dx.doi.org/10.1016/j.trim.2011.02.002},
  volume       = {24},
  year         = {2011},
}