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CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergistically suppress accelerated rejection and prolong cardiac allograft survival in mice.

Shao, Wei; Yan, Guoliang; Lin, Yingying; Chen, Jibing; Dai, Helong; Wang, Feng; Xi, Yanfeng; Thorlacius, Henrik LU and Qi, Zhongquan LU (2011) In Scandinavian Journal of Immunology 74. p.430-437
Abstract
Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1... (More)
Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti-CD154/LFA-1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft-infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL-10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Immunology
volume
74
pages
430 - 437
publisher
Wiley-Blackwell
external identifiers
  • WOS:000296081100002
  • PMID:21707692
  • Scopus:80053489224
ISSN
1365-3083
DOI
10.1111/j.1365-3083.2011.02595.x
language
English
LU publication?
yes
id
54fd6aec-38a9-4c5a-953e-24d89c3b8a1d (old id 2007726)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21707692?dopt=Abstract
date added to LUP
2011-07-06 11:12:51
date last changed
2017-01-01 07:45:50
@article{54fd6aec-38a9-4c5a-953e-24d89c3b8a1d,
  abstract     = {Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti-CD154/LFA-1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft-infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL-10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection.},
  author       = {Shao, Wei and Yan, Guoliang and Lin, Yingying and Chen, Jibing and Dai, Helong and Wang, Feng and Xi, Yanfeng and Thorlacius, Henrik and Qi, Zhongquan},
  issn         = {1365-3083},
  language     = {eng},
  pages        = {430--437},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergistically suppress accelerated rejection and prolong cardiac allograft survival in mice.},
  url          = {http://dx.doi.org/10.1111/j.1365-3083.2011.02595.x},
  volume       = {74},
  year         = {2011},
}