Expression of Histocompatibility 2 Blastocyst (H2-Bl) in embryonic stem cells inhibits CD8+ T-cell activation but is not sufficient to facilitate graft tolerance

Dingwell, Steven, Brooks, Andrew, Apte, Simon H., Waters, Mike, Lavin, Martin F. and Wolvetang, Ernst J. (2015) Expression of Histocompatibility 2 Blastocyst (H2-Bl) in embryonic stem cells inhibits CD8+ T-cell activation but is not sufficient to facilitate graft tolerance. Journal of Stem Cell Research and Therapy, 5 12: 1000320.1-1000320.8. doi:10.4172/2157-7633.1000320


Author Dingwell, Steven
Brooks, Andrew
Apte, Simon H.
Waters, Mike
Lavin, Martin F.
Wolvetang, Ernst J.
Title Expression of Histocompatibility 2 Blastocyst (H2-Bl) in embryonic stem cells inhibits CD8+ T-cell activation but is not sufficient to facilitate graft tolerance
Journal name Journal of Stem Cell Research and Therapy   Check publisher's open access policy
ISSN 2157-7633
Publication date 2015
Sub-type Article (original research)
DOI 10.4172/2157-7633.1000320
Open Access Status DOI
Volume 5
Issue 12
Start page 1000320.1
End page 1000320.8
Total pages 8
Place of publication Los Angeles, CA, United States
Publisher Omics Publishing
Collection year 2016
Language eng
Formatted abstract
Universal embryonic stem cell donor lines would greatly facilitate stem cell based regenerative medicine and permit facile testing of human pluripotent stem cell derived grafts in xenogeneic settings. Because HLA-G overcomes immune cell mediated attack of foetal tissues during pregnancy and inhibits T-cell responses and dendritic cell antigen maturation in vitro and in vivo, it is an attractive candidate molecule for achieving this goal. Here we investigated whether enforced expression of either the soluble or the membrane bound form of the HLA-G mouse homologue, H2- Bl, in human and mouse ES cell lines would allow engraftment in immunocompetent mice. Despite evidence for robust expression of soluble or membrane bound H2-Bl molecules and effective inhibition of CD8+ T-cell proliferation by all H2-Bl engineered ES cell lines, all failed to generate teratomas in immunocompetent mice, despite doing so in NODSCID mice. We conclude that expression of H2-Bl in human and mouse embryonic stem cells alone is insufficient to overcome xenogeneic rejection.
Keyword Human embryonic stem cells
Mouse embryonic stem cells
HLA-G
H2-Bl
Immune tolerance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Sun, 24 Jan 2016, 11:38:32 EST by Andrew Brooks on behalf of Institute for Molecular Bioscience