The specific aims of our research are: (1) to explore and apply further the newly discovered role of natural killer cells as mediators of natural hybrid (genetic) resistance to parental marrow transplantation (the NK-HR connection) and its apparent normal function as an anti-lymphoma-leukemia mechanism by determining whether RadLV or other MuLV antigens represent the targets of both NK cells versus radiation lymphomas and of F?1? NK cells versus parental bone marrow and lymphoma transplantation; (2) to explore and apply further the recent success in converting the AKR strain from a low NK-high spontaneous leukemia strain to a high NK-relatively low leukemia strain by adoptive transfer of bone marrow from a high NK-low leukemia marrow donor, and to seek more clinically applicable means of achieving the same result by selected long-term stimulators of NK cell activity; (3) to explore the apparent role of cytoskeletal microtubules in the NK-target cell lytic mechanism and the possible role of cytoskeletal microfilaments in the NK-target cell-binding process; (4) to develop NK 1.1 antibody-producing cloned hybridoma cell lines from high-titered NK 1.1 antibody-producing mice; and (5) to explore in mouse strains the reported positive correlation of human bone marrow recipient pretransplant NK-cell level with the subsequent development of GVHD. Long-term goals include developing knowledge and methods applicable to: (1) the prevention or therapy of human lymphoma-leukemia or other tumors; (2) improved use of human bone marrow transplantation for treatment of leukemia and other diseases with reference to the role of donor NK levels in conferring resistance to leukemia and the role of recipient NK levels with reference to GVHD; and (3) whether a human equivalent of NK cell-mediated genetic resistance to marrow transplantation may account for some of the failures of HLA-compatible human marrow transplants to take. (SR)
| Ide, H; Kow, Y W; Wallace, S S (1985) Thymine glycols and urea residues in M13 DNA constitute replicative blocks in vitro. Nucleic Acids Res 13:8035-52 |
