HOMING AND IMMUNOGENICITY OF MURINE STROMAL CELLS TRANSFECTED WITH XENOGENEIC MHC CLASS-II GENES

Syngeneic (murine) and xenogeneic (canine) marrow-derived stromal cell s were injected intravenously into SCID and normal mice to examine the homing pattern and persistence of these cells in vivo, By in situ hyb ridization, these stromal cells were detectable in the bone marrow cav ity and the spleen 21 days after injection. Xenogeneic cells did not p ersist 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 tr ansplanted 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 c ells 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 xeno geneic stromal cells to hemopoietic organs and for prolonged persisten ce, 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 h ome to spleen and marrow and persisted even though the recipient had b ecome sensitized, Their survival may be due to a loss of expression of the transfected gene, Alternatively, the presentation of these xenoge neic gene products in the hemopoietic organs was such that a cytotoxic response was not induced, These results also show that stromal cells can serve as a vehicle for gene delivery, conceivably with the possibi lity of organ targeting.