biostudies-literaturede Almeida PENIBIB NIH HHSNIAID NIH HHSNHLBI NIH HHS3903https://www.ebi.ac.uk/biostudies/studies/S-EPMC4075468biostudies-literatureUnknown5The exact nature of the immune response elicited by autologous-induced pluripotent stem cell (iPSC) progeny is still not well understood. Here we show in murine models that autologous iPSC-derived endothelial cells (iECs) elicit an immune response that resembles the one against a comparable somatic cell, the aortic endothelial cell (AEC). These cells exhibit long-term survival in vivo and prompt a tolerogenic immune response characterized by elevated IL-10 expression. In contrast, undifferentiated iPSCs elicit a very different immune response with high lymphocytic infiltration and elevated IFN-γ, granzyme-B and perforin intragraft. Furthermore, the clonal structure of infiltrating T cells from iEC grafts is statistically indistinguishable from that of AECs, but is different from that of undifferentiated iPSC grafts. Taken together, our results indicate that the differentiation of iPSCs results in a loss of immunogenicity and leads to the induction of tolerance, despite expected antigen expression differences between iPSC-derived versus original somatic cells.Nature communicationsTransplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance.PMC4075468K08 HL119590T32 EB009035R01 AI085575U01 HL099776Longaker MTHu SOdegaard JLo DWu JCEbert ADiecke SSanchez-Freire VNegrin RSDey DKooreman NGBrouwer TPMontoro DTMordwinkin NMMeyer EHde Almeida PEfalseTransplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance.The exact nature of the immune response elicited by autologous-induced pluripotent stem cell (iPSC) progeny is still not well understood. Here we show in murine models that autologous iPSC-derived endothelial cells (iECs) elicit an immune response that resembles the one against a comparable somatic cell, the aortic endothelial cell (AEC). These cells exhibit long-term survival in vivo and prompt a tolerogenic immune response characterized by elevated IL-10 expression. In contrast, undifferentiated iPSCs elicit a very different immune response with high lymphocytic infiltration and elevated IFN-γ, granzyme-B and perforin intragraft. Furthermore, the clonal structure of infiltrating T cells from iEC grafts is statistically indistinguishable from that of AECs, but is different from that of undifferentiated iPSC grafts. Taken together, our results indicate that the differentiation of iPSCs results in a loss of immunogenicity and leads to the induction of tolerance, despite expected antigen expression differences between iPSC-derived versus original somatic cells.2014-01-01T00:00:00Z2014 May2024-11-21T07:00:08.105Z2019-03-27T01:31:03ZS-EPMC40754682487516410.1038/ncomms4903