Suppressing memory T cell activation induces islet allograft tolerance in alloantigen-primed mice
(2010) In Transplant International 23(11). p.1154-1163- Abstract
- P>Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4+ memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8+ memory T cells. In the alloantigen-primed model, use of anti-CD134L and anti-CD122 mAbs in addition to co-stimulatory blockade with anti-CD154 and anti-LFA-1... (More)
- P>Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4+ memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8+ memory T cells. In the alloantigen-primed model, use of anti-CD134L and anti-CD122 mAbs in addition to co-stimulatory blockade with anti-CD154 and anti-LFA-1 prolonged secondary allograft survival and significantly reduced the proportion of memory T cells; meanwhile, this combination therapy increased the proportion of regulatory T cells (Tregs) in the spleen, inhibited lymphocyte infiltration in the graft, and suppressed alloresponse of recipient splenic T cells. However, we also detected high levels of alloantibodies in the serum which caused high levels of damage to the allogeneic spleen cells. Our results suggest that combination of four mAbs can significantly suppress the function of memory T cells and prolong allograft survival in alloantigen primed animals. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1726287
- author
- Xia, Junjie ; Chen, Jibing ; Shao, Wei ; Lan, Tianshu ; Wang, Yongzhi ; Xie, Baiyi ; Thorlacius, Henrik LU ; Tian, Feng ; Huang, Ruxin and Qi, Zhongquan
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- islet transplantation, anti-CD122, alloantigens, anti-CD134L, memory T, cells
- in
- Transplant International
- volume
- 23
- issue
- 11
- pages
- 1154 - 1163
- publisher
- Springer
- external identifiers
-
- wos:000282422600013
- scopus:77957555827
- pmid:20536791
- ISSN
- 1432-2277
- DOI
- 10.1111/j.1432-2277.2010.01106.x
- language
- English
- LU publication?
- yes
- id
- 57d14152-91c8-4746-af5e-0effc90cdfee (old id 1726287)
- date added to LUP
- 2016-04-01 14:40:24
- date last changed
- 2022-01-28 01:52:40
@article{57d14152-91c8-4746-af5e-0effc90cdfee,
abstract = {{P>Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4+ memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8+ memory T cells. In the alloantigen-primed model, use of anti-CD134L and anti-CD122 mAbs in addition to co-stimulatory blockade with anti-CD154 and anti-LFA-1 prolonged secondary allograft survival and significantly reduced the proportion of memory T cells; meanwhile, this combination therapy increased the proportion of regulatory T cells (Tregs) in the spleen, inhibited lymphocyte infiltration in the graft, and suppressed alloresponse of recipient splenic T cells. However, we also detected high levels of alloantibodies in the serum which caused high levels of damage to the allogeneic spleen cells. Our results suggest that combination of four mAbs can significantly suppress the function of memory T cells and prolong allograft survival in alloantigen primed animals.}},
author = {{Xia, Junjie and Chen, Jibing and Shao, Wei and Lan, Tianshu and Wang, Yongzhi and Xie, Baiyi and Thorlacius, Henrik and Tian, Feng and Huang, Ruxin and Qi, Zhongquan}},
issn = {{1432-2277}},
keywords = {{islet transplantation; anti-CD122; alloantigens; anti-CD134L; memory T; cells}},
language = {{eng}},
number = {{11}},
pages = {{1154--1163}},
publisher = {{Springer}},
series = {{Transplant International}},
title = {{Suppressing memory T cell activation induces islet allograft tolerance in alloantigen-primed mice}},
url = {{http://dx.doi.org/10.1111/j.1432-2277.2010.01106.x}},
doi = {{10.1111/j.1432-2277.2010.01106.x}},
volume = {{23}},
year = {{2010}},
}