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Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart

Grinnemo, Karl-Henrik; Genead, Rami; Kumagai-Braesch, Makiko; Andersson, Agneta; Danielsson, Christian; Mansson-Broberg, Agneta; Dellgren, Goran; Stromberg, Anne-Marie; Ekberg, Henrik LU and Hovatta, Outi, et al. (2008) In Stem Cells 26(7). p.1850-1857
Abstract
In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated... (More)
In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice. (Less)
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published
subject
keywords
tolerance, human embryonic stem cells, Foxp3(+) T-cells, CTLA4Ig, anti-CD40L, anti-LFA-1
in
Stem Cells
volume
26
issue
7
pages
1850 - 1857
publisher
AlphaMed Press
external identifiers
  • wos:000258004400020
  • scopus:55049129491
ISSN
1549-4918
DOI
10.1634/stemcells.2008.0111
language
English
LU publication?
yes
id
7eb4377f-6f02-4fd7-adc0-f6bef2c935ad (old id 1252966)
date added to LUP
2008-10-31 10:31:55
date last changed
2018-01-07 07:01:28
@article{7eb4377f-6f02-4fd7-adc0-f6bef2c935ad,
  abstract     = {In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.},
  author       = {Grinnemo, Karl-Henrik and Genead, Rami and Kumagai-Braesch, Makiko and Andersson, Agneta and Danielsson, Christian and Mansson-Broberg, Agneta and Dellgren, Goran and Stromberg, Anne-Marie and Ekberg, Henrik and Hovatta, Outi and Sylven, Christer and Corbascio, Matthias},
  issn         = {1549-4918},
  keyword      = {tolerance,human embryonic stem cells,Foxp3(+) T-cells,CTLA4Ig,anti-CD40L,anti-LFA-1},
  language     = {eng},
  number       = {7},
  pages        = {1850--1857},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart},
  url          = {http://dx.doi.org/10.1634/stemcells.2008.0111},
  volume       = {26},
  year         = {2008},
}