Homing and immunogenicity of murine stromal cells transfected with xenogeneic MHC class II genes.
Syngeneic (murine) and xenogeneic (canine) marrow-derived stromal cells were injected intravenously into SCID and normal mice to examine the homing pattern and persistence of these cells in vivo. By in situ hybridization, these stromal cells were detectable in the bone marrow cavity and the spleen 21 days after injection. Xenogeneic cells did not persist in normal mice but persisted in SCID mice. Conditioning of the recipients with irradiation or 5-fluorouracil (5-FU) treatment did not alter these results. In addition, syngeneic murine stromal cells were transfected with the genes for canine MHC class II (DRA + DRB) and transplanted into murine recipients to investigate their homing pattern and immunogenicity. These transfected syngeneic stromal cells did also home to marrow and spleen even in normal recipients. However, these cells led to sensitization of the host towards canine antigens as shown by accelerated skin graft rejection and delayed type hypersensitivity (DTH). Thus, immunodeficient (SCID) mice allow for the homing of xenogeneic stromal cells to hemopoietic organs and for prolonged persistence. In immunocompetent (normal) mice, no xenogeneic stromal cells were identified in spleen and marrow, either because of their inability to home or more likely because of immunological rejection. In contrast, syngeneic stromal cells expressing xenogeneic MHC class II genes did home to spleen and marrow and persisted even though the recipient had become sensitized. Their survival may be due to a loss of expression of the transfected gene. Alternatively, the presentation of these xenogeneic gene products in the hemopoietic organs was such that a cytotoxic response was not induced.(ABSTRACT TRUNCATED AT 250 WORDS)
Programs in Transplantation Biology, Pediatric Oncology, and Pathology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
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Huss
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Smith
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Myerson
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Deeg
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement; D004285:Dogs; D018014:Gene Transfer Techniques; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D017154:Stromal Cells / Q000276:immunology* / Q000637:transplantation; D014162:Transfection; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II