title: Perforin- and Fas-mediated cytotoxic pathways are not required for allogeneic resistance to bone marrow grafts in mice.
abstract: Failure to engraft is a major complication in allogeneic bone marrow transplantation (BMT) using T cell-depleted donor marrow. Previous work has demonstrated that radioresistant host natural killer (NK) cells, CD8+ T cells, and T cells with NK markers participate in the active rejection of donor hematopoietic stem cells in murine models of allogeneic BMT. However, the precise role of cell-mediated cytotoxic mechanisms in marrow allograft rejection remains controversial. To determine the role of perforin- and Fas-mediated cytotoxicity in allogeneic resistance, we transplanted T cell-depleted allogeneic bone marrow into perforin-deficient (perforin 0/0), Fas-ligand-defective (gld/gld), and normal mice. Short-term resistance was measured using a sensitive in vitro assay for colony formation by spleen cells from BMT recipients. The findings we report here demonstrate that strong allogeneic resistance remains largely intact in perforin-deficient and Fas-ligand-defective recipient mice. Thus, perforin- and Fas-mediated cytotoxic pathways are not required for resistance to bone marrow allografts in mice. We conclude that alternative pathways of cytotoxicity and/or soluble factors can mediate resistance to allogeneic BM.
authors.affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Baker
authors.forename: E R
authors.initials: ER
authors.lastname: Podack
authors.forename: R B
authors.initials: RB
authors.lastname: Levy
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin