My laboratory is involved in studies of murine bone marrow transplantation (BMT) and natural killer (NK) cells. NK cells, unlike T or B cells, fail to rearrange TCR or Ig receptor genes and, therefore, do not have a vast repertoire of receptors. The receptors recently discovered, however, do recognize and bind to MHC class I molecules. Rather than killing target cells after this recognition event, a ?negative signal? is transmitted to the NK cells. A failure to receive the negative signal allows the NK cell to kill through positive signals. We are analyzing these activating receptors and how they regulate the ability of mice to reject bone marrow grafts. In addition, we are developing a model system of treatment of leukemia by blocking the negative signals that NK cells receive from class I molecule; this allows NK cells to lyse autologous tumor cells very well. T cell depletion of marrow grafts prevents severe graft-v-host disease but makes the marrow grafts very sensitive to rejection. Clinically applicable approaches are used to induce `tolerance' to allogeneic marrow grafts to allow the use of T cell depletion safely.
