Advanced

Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice.

Wang, Feiyu; Xia, Junjie; Chen, Jibing; Peng, Yuanzheng; Cheng, Panpan; Ekberg, Henrik LU ; Wang, Xiaomin and Qi, Zhongquan LU (2010) In Xenotransplantation 17(6). p.460-468
Abstract
Wang F, Xia J, Chen J, Peng Y, Cheng P, Ekberg H, Wang X, Qi Z. Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice. Xenotransplantation 2010; 17: 460-468. © 2010 John Wiley & Sons A/S. Abstract: Background: Donor-reactive memory T cells are known to accelerate allograft rejection; in our previous study, we reported that combined monoclonal antibodies (mAbs) could prolong islet allograft survival in alloantigen-primed mice. In this study, we examine the effects of donor-reactive memory T cells on the xenograft survival and methods to prolong the islet graft survival. Methods: To collect donor-reactive T cells, we performed full-thickness rat skin xenografting on BALB/c mice and... (More)
Wang F, Xia J, Chen J, Peng Y, Cheng P, Ekberg H, Wang X, Qi Z. Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice. Xenotransplantation 2010; 17: 460-468. © 2010 John Wiley & Sons A/S. Abstract: Background: Donor-reactive memory T cells are known to accelerate allograft rejection; in our previous study, we reported that combined monoclonal antibodies (mAbs) could prolong islet allograft survival in alloantigen-primed mice. In this study, we examine the effects of donor-reactive memory T cells on the xenograft survival and methods to prolong the islet graft survival. Methods: To collect donor-reactive T cells, we performed full-thickness rat skin xenografting on BALB/c mice and isolated the T cells from the mice after 6-8 weeks. These cells were then adoptively transferred to syngenic mice 1 day before rat-to-mouse islet transplantation. Three experimental groups were established in the adoptive transfer model: recipient mice treated with isotype mAbs (isotype group); mice treated with anti-CD40L mAb (anti-CD40L group); and mice treated with anti-CD40L, anti-OX40L, and anti-CD122 mAbs (3-combined group). Results: Lewis rat islet xenografts transplanted in naïve mice showed a mean survival time (MST) of 12.8 days, while the graft rejection was accelerated if the recipient mice were treated with adoptively transferred donor-reactive T cells (MST, 8.67 days). Treatment with anti-CD40L mb could not reverse the accelerated rejection (MST, 9.3 days). However, when anti-CD40L mb was combined with anti-OX40L and anti-CD122 mAbs, there was a considerable increase in the MST, which was 72.2 days. Compared to the isotype group, the 3-combined group had significantly lesser proportion of memory T cells and greater proportion of regulatory T cells (Tregs) in the spleen. Meanwhile, in the 3-combined group, the production of anti-rat antibodies was markedly inhibited. Conclusion: Treatment with a combination of antibodies could significantly reverse the accelerated rejection mediated by donor-reactive memory T cells by inhibiting cellular and humoral immune responses. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Xenotransplantation
volume
17
issue
6
pages
460 - 468
publisher
Wiley-Blackwell
external identifiers
  • WOS:000285390200010
  • PMID:21158947
  • Scopus:78650641856
ISSN
0908-665X
DOI
10.1111/j.1399-3089.2010.00618.x
language
English
LU publication?
yes
id
5d0fc52b-b1dc-45ca-b342-c85736e3426a (old id 1756348)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21158947?dopt=Abstract
date added to LUP
2011-01-03 15:27:42
date last changed
2017-01-01 07:51:44
@article{5d0fc52b-b1dc-45ca-b342-c85736e3426a,
  abstract     = {Wang F, Xia J, Chen J, Peng Y, Cheng P, Ekberg H, Wang X, Qi Z. Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice. Xenotransplantation 2010; 17: 460-468. © 2010 John Wiley & Sons A/S. Abstract: Background: Donor-reactive memory T cells are known to accelerate allograft rejection; in our previous study, we reported that combined monoclonal antibodies (mAbs) could prolong islet allograft survival in alloantigen-primed mice. In this study, we examine the effects of donor-reactive memory T cells on the xenograft survival and methods to prolong the islet graft survival. Methods: To collect donor-reactive T cells, we performed full-thickness rat skin xenografting on BALB/c mice and isolated the T cells from the mice after 6-8 weeks. These cells were then adoptively transferred to syngenic mice 1 day before rat-to-mouse islet transplantation. Three experimental groups were established in the adoptive transfer model: recipient mice treated with isotype mAbs (isotype group); mice treated with anti-CD40L mAb (anti-CD40L group); and mice treated with anti-CD40L, anti-OX40L, and anti-CD122 mAbs (3-combined group). Results: Lewis rat islet xenografts transplanted in naïve mice showed a mean survival time (MST) of 12.8 days, while the graft rejection was accelerated if the recipient mice were treated with adoptively transferred donor-reactive T cells (MST, 8.67 days). Treatment with anti-CD40L mb could not reverse the accelerated rejection (MST, 9.3 days). However, when anti-CD40L mb was combined with anti-OX40L and anti-CD122 mAbs, there was a considerable increase in the MST, which was 72.2 days. Compared to the isotype group, the 3-combined group had significantly lesser proportion of memory T cells and greater proportion of regulatory T cells (Tregs) in the spleen. Meanwhile, in the 3-combined group, the production of anti-rat antibodies was markedly inhibited. Conclusion: Treatment with a combination of antibodies could significantly reverse the accelerated rejection mediated by donor-reactive memory T cells by inhibiting cellular and humoral immune responses.},
  author       = {Wang, Feiyu and Xia, Junjie and Chen, Jibing and Peng, Yuanzheng and Cheng, Panpan and Ekberg, Henrik and Wang, Xiaomin and Qi, Zhongquan},
  issn         = {0908-665X},
  language     = {eng},
  number       = {6},
  pages        = {460--468},
  publisher    = {Wiley-Blackwell},
  series       = {Xenotransplantation},
  title        = {Combination of antibodies inhibits accelerated rejection mediated by memory T cells in xenoantigen-primed mice.},
  url          = {http://dx.doi.org/10.1111/j.1399-3089.2010.00618.x},
  volume       = {17},
  year         = {2010},
}