Stem cell transplantation across major genetic barriers.

Megadose haploidentical transplants, mismatched at three HLA loci, engraft rapidly and durably without induction of graft-versus-host disease (GVHD). In vitro studies suggest that veto cells, contained in the population of hematopoietic progenitors, facilitate this favorable outcome. Cytotoxic T cells, not reactive against the recipient but reactive against a third party, are potent veto cells and can synergize with the stem cells and facilitate allogeneic bone marrow engraftment without GVHD. Experiments with mice deficient in FasL and Fas, with transfer of FasL gene and with anti-CD8 antibody, suggest that the veto activity associated with cytotoxic T lymphocytes (CTLs) requires simultaneous expression of FasL and CD8.