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Combined Costimulation Blockade Inhibits Accelerated Rejection Mediated by Alloantigen-primed Memory T Cells in Mice

Xie, Baiyi ; Chen, Jibing ; Xia, Junjie ; Wang, Yongzhi ; Liang, Hua ; Ekberg, Henrik LU ; Corbascio, Matthias and Qi, Zhongquan (2009) In Immunological Investigations 38(7). p.639-651
Abstract
Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.17 days in the untreated group, 10.33 days in the CTLA4Ig- and antiCD40L- treated (2-combined) group, and more than 100 days in the CTLA4Ig-, anti-CD40L-, anti-LFA-1-, and anti-OX40L-treated (4-combined) group. Histological analysis revealed that the mean rejection level was Grade 4 in the untreated group, Grade 3 in the 2-combined treatment group, and Grade 0 in the... (More)
Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.17 days in the untreated group, 10.33 days in the CTLA4Ig- and antiCD40L- treated (2-combined) group, and more than 100 days in the CTLA4Ig-, anti-CD40L-, anti-LFA-1-, and anti-OX40L-treated (4-combined) group. Histological analysis revealed that the mean rejection level was Grade 4 in the untreated group, Grade 3 in the 2-combined treatment group, and Grade 0 in the 4-combined treatment group. CD44(high) T cells were detected only in the untreated group. The in vitro proliferation of lymphocytes of both untreated and 2-combined group was higher than that of the 4-combined treatment group (p < 0.01). Compared with the untreated group, the expression levels of IL-2, IFN-gamma, and Foxp3 were lower in the 2-combined treatment group; the expression levels of these genes were the lowest in the 4-combined treatment group. IL-10 expression was significantly higher in the 4-combined treatment group than in the other groups. These results demonstrate the inhibition efficacy of combined costimulation blockade in accelerated-rejection models and the possible mechanisms underlying the suppression of cellular immunity in mice receiving grafts as well as in inducing the activation of IL-10-producing Tr1 cells in grafts. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immunological tolerance, transplantation, Cardiac, Memory T cells, Costimulation blockade, Accelerated rejection
in
Immunological Investigations
volume
38
issue
7
pages
639 - 651
publisher
Taylor & Francis Group LLC Philadelphia
external identifiers
  • wos:000271275000007
  • scopus:70350683734
ISSN
0882-0139
DOI
10.1080/08820130903062228
language
English
LU publication?
yes
id
71609a32-c44d-4e05-8ed5-42019274c6c7 (old id 1505085)
date added to LUP
2016-04-01 13:42:10
date last changed
2025-04-04 15:26:53
@article{71609a32-c44d-4e05-8ed5-42019274c6c7,
  abstract     = {{Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.17 days in the untreated group, 10.33 days in the CTLA4Ig- and antiCD40L- treated (2-combined) group, and more than 100 days in the CTLA4Ig-, anti-CD40L-, anti-LFA-1-, and anti-OX40L-treated (4-combined) group. Histological analysis revealed that the mean rejection level was Grade 4 in the untreated group, Grade 3 in the 2-combined treatment group, and Grade 0 in the 4-combined treatment group. CD44(high) T cells were detected only in the untreated group. The in vitro proliferation of lymphocytes of both untreated and 2-combined group was higher than that of the 4-combined treatment group (p &lt; 0.01). Compared with the untreated group, the expression levels of IL-2, IFN-gamma, and Foxp3 were lower in the 2-combined treatment group; the expression levels of these genes were the lowest in the 4-combined treatment group. IL-10 expression was significantly higher in the 4-combined treatment group than in the other groups. These results demonstrate the inhibition efficacy of combined costimulation blockade in accelerated-rejection models and the possible mechanisms underlying the suppression of cellular immunity in mice receiving grafts as well as in inducing the activation of IL-10-producing Tr1 cells in grafts.}},
  author       = {{Xie, Baiyi and Chen, Jibing and Xia, Junjie and Wang, Yongzhi and Liang, Hua and Ekberg, Henrik and Corbascio, Matthias and Qi, Zhongquan}},
  issn         = {{0882-0139}},
  keywords     = {{Immunological tolerance; transplantation; Cardiac; Memory T cells; Costimulation blockade; Accelerated rejection}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{639--651}},
  publisher    = {{Taylor & Francis Group LLC Philadelphia}},
  series       = {{Immunological Investigations}},
  title        = {{Combined Costimulation Blockade Inhibits Accelerated Rejection Mediated by Alloantigen-primed Memory T Cells in Mice}},
  url          = {{http://dx.doi.org/10.1080/08820130903062228}},
  doi          = {{10.1080/08820130903062228}},
  volume       = {{38}},
  year         = {{2009}},
}