MARROW GRAIT FAILURE IN ALLOGENIC BONE MARROW TRANSPLANTATION

许多观察表明，宿主淋巴细胞，

A number of observations have suggested that host lymohocytes, specifically cytotoxic T cells (CTL) may play a significant role in mediating allogeneic marrow graft rejection. In a murine model system, CTL were cloned from the spleens of sublethally irradiated animals which had rejected MHC disparate marrow grafts. It was found that cloned CTL were sufficient to effect rejection of T cell depleted allogeneic marrow in lethally irradiated animals. The rejection of marrow grafts by CTL was specific for the MHC gene products expressed by the marrow cells and correlated with the cytotoxic specificity of the individual clones. Although CTL can therefore reject marrow grafts, the administration of anti-CD3 monoclonal antibody in vivo has to date not enhanced engraftment of T cell depleted marrow in sublethally irradiated murine hosts. Cloned xenospecific human CTL were also directly evaluated for their ability to mediate tissue damage in vivo and were found to mediate tissue injury with specificity for MHC antigens of the murine host. The fine specificity of xeno-antigen recognition by human T cells suggests that in transplantation of xenogeneic tissue, as in transplantation of MHC mismatched allogeneic tissue, the particular tissue antigens, and therefore tissue typing, may be a relevant consideration. The generation of human CTL has been characterized and certain essential cellular interactions in that generation have been identified. In addition, the mechanisms for the blocking effects of monoclonal antibodies specific for the CD2 (sheep red blood cell recoptor), CD8, and CD18 (LFA-1) molecules expressed on the surface of human CTL have been investigated. Results indicate that the inhibition by anti-CD2 antibody did not occur in the absence of target cells, consistent with the interpretation that this antibody exerts its blocking effect by interfering with a CD2 ligand interaction. However, results with anti-CD8 and anti-CD18 monoclonal antibodies indicated that inhibition by these agents could not be explained by simple disruption of a T cell receptor-target cell ligand interaction.