Expression of Histocompatibility 2 Blastocyst (H2-Bl) in Embryonic Stem Cells Inhibits CD8+ T-Cell Activation but is not Sufficient to Facilitate Graft Tolerance

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 NOD-SCID mice. We conclude that expression of H2-Bl in human and mouse embryonic stem cells alone is insufficient to overcome xenogeneic rejection.