title: Human embryonic stem cells are immunogenic in allogeneic and xenogeneic settings.
abstract: Recent studies have suggested that human embryonic stem cells (HESC) are immune-privileged and may thereby circumvent rejection. The expression of immunologically active molecules was studied by DNA microarray analysis and by flow cytometry. HESC were transplanted into immunologically competent mice and traced by fluorescence in-situ hybridization (FISH) and immunohistochemistry. The ability of HESC to directly and indirectly induce immune responses in CD4+ T-cells from naive and transplanted mice was studied. Their ability to induce immune responses of human CD4+ T-cells, when cultured in the presence of dendritic cells (DC) syngeneic to responder T-cells, was also analysed. HESC demonstrated expression of HLA class I and HLA class II genes, but the cell surface expression of HLA class II molecules was low even after incubation with IFNgamma. In wild-type mice, HESC could be demonstrated by FISH until 3 days after transplantation and were surrounded by heavy infiltrates of T-cells and macrophages. HESC induced a similar immune response as human fibroblast cells (HFib) on naive and immunized T-cells, both directly and in the presence of syngeneic DC. A similar response was observed in the allogeneic setting. It is concluded that HESC are immunologically inert and do not inhibit immune responses during direct or indirect antigen presentation, and they were acutely rejected in a xenogeneic setting.
authors.affiliation: Department of Cardiothoracic Surgery and Anaesthesiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Grinnemo
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai-Braesch
authors.forename: Agneta
authors.initials: A
authors.lastname: Månsson-Broberg
authors.forename: Heli
authors.initials: H
authors.lastname: Skottman
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Hao
authors.forename: Anwar
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Agneta
authors.initials: A
authors.lastname: Andersson
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Strömberg
authors.forename: Riita
authors.initials: R
authors.lastname: Lahesmaa
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
authors.forename: Christer
authors.initials: C
authors.lastname: Sylven
authors.forename: Matthias
authors.initials: M
authors.lastname: Corbascio
authors.forename: Göran
authors.initials: G
authors.lastname: Dellgren
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured / Q000276:immunology; D053595:Embryonic Stem Cells / Q000276:immunology* / Q000637:transplantation; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens