Perforin- and Fas-mediated cytotoxic pathways are not required for allogeneic resistance to bone marrow grafts in mice.

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.