Inhibition of hybrid resistance by 5-fluorouracil. Destruction of a Thy-1+ Lyt-1+2- spleen cell implicated in the expression of hybrid resistance.
Hybrid resistance designates the poor proliferation of parent-strain bone marrow cells injected into lethally irradiated hybrids. While testing a variety of oncostatic drugs for their capacity to inhibit hybrid resistance, we found that 5-fluorouracil (5-FU) injected into B6D2F1 hybrids three days before grafting enhances the growth of parent-strain B6 bone marrow cells. Hybrid resistance can be restored in these 5-FU-treated B6D2F1 recipients by the injection of spleen cells from untreated (normal) B6D2F1 mice. Treatment of these normal B6D2F1 spleen cells with anti-Thy-1 or anti-Lyt-1 antibodies plus complement abolishes their capacity to restore resistance, whereas treatment with anti Lyt-2 antibody plus complement has no effect. It is known that the rejection of parent-strain bone marrow cells by the F1 hybrid is a multistep process in which more than one cell type is involved, and that the final effector cell is asialo-GMI+, cyclophosphamide-sensitive, and responsive to IFN (possibly the natural killer cell). The Thy-1+Lyt-1+2- spleen cell we describe here, which is eliminated by the 5-FU, doesn't seem to be the final effector cell for hybrid resistance since transfer of spleen cells from cyclophosphamide-treated (final-effector-cell-depleted) B6D2F1 hybrids into 5-FU treated B6D2F1 mice restores hybrid resistance just as well as do normal B6D2F1 spleen cells; and, when injected into 5-FU-treated B6D2F1 hybrids, the IFN inducer pI:pC also restores resistance. The cell we now describe would be a third cell type, probably responsible for the initial recognition of grafted parent-strain bone marrow cells, which triggers the mechanism of hybrid resistance. This hypothesis could explain the observed specificity of parent-strain bone marrow graft rejection by F1 hybrids.
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects; D006824:Hybridization, Genetic; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000950:Antigens, Ly; D000954:Antigens, Surface; D018800:Thy-1 Antigens; D005472:Fluorouracil