Natural Killer Cells Overcome Rejection

Abstract

Reconstitution of the hematopoietic system by bone marrow (BM) transplantation operates on a knife-edge. Engraftment can be improved by allowing some degree of mismatch between the tissue antigens of the donor and recipient and, in diseases such as leukemia, also provides a powerful means for helping destroy host-derived leukemic cells. However, the greater the mismatch, the more vigorously residual T cells in the donor BM will react against the recipient tissues, leading to graft-versus-host disease (GVHD). Two reports address how natural killer (NK) cells help prevent rejection (see the Perspective by Kärre). Rugerri et al. observed that for NK cells, a greater level of NK cell reactivity against host antigens correlated with a higher incidence of successful transplantation. In mice, preconditioning with purified host-reactive NK cells removed the need for the usual preablation of recipient bone marrow by irradiation, and these animals did not develop T cell-mediated GVHD seen in control mice. Host-reactive NK cells may ablate antigen-presenting cells in the host and, in so doing, prevent them from inducing anti-host T cells. Activation of NK cells can also be prevented by ligands that bind inhibitory receptors on the NK cell surface. Wang et al. observed that in mice lacking the phosphatase SH-2-containing inositol phosphatase (SHIP), the repertoire of inhibitory NK receptors was skewed in favor of select receptors that could recognize foreign, as well as self, ligands. When transplanted with bone marrow, these mice failed to reject bone marrow from a mismatched donor. Incidence of GVHD was also absent in these mice, suggesting a possible role for host-derived NK cells in GVHD. K. Kärre, A perfect mismatch. Science 295 , 2029-2031 (2002). [Abstract] [Full Text] L. Ruggeri, M. Capanni, E. Urbani, K. Perruccio, W. D. Shlomchik, A. Tosti, S. Posati, D. Rogaia, F. Frassoni, F. Aversa, M. F. Martelli, A. Velardi, Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295 , 2097-2100 (2002). [Abstract] [Full Text] J.-W. Wang, J. M. Howson, T. Ghansah, C. Desponts, J. M. Ninos, S. L. May, K. H. T. Nguyen, N. Toyama-Sorimachi, W. G. Kerr, Influence of SHIP on the NK repertoire and allogeneic bone marrow transplantation. Science 295 , 2094-2097 (2002). [Abstract] [Full Text]