Immunobiology of natural killer cells and bone marrow transplantation: merging of basic and preclinical studies

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Abstract
Summary: Natural killer (NK) cells mediate acute rejection of bone marrow, but not solid tissue, allografts in lethally irradiated mice. Precisely how and why this rejection occurs is still unclear. In allogeneic bone marrow transplantation (BMT), a spectrum of results is possible; one result can be marrow graft failure due to host rejection of the graft by NK and T cells and, at the opposite spectrum, the occurrence of graft‐versus‐host disease (GVHD). Donor NK cells, however, appear capable of improving donor engraftment without giving rise to GVHD and thus may be of use as an immunotherapy following BMT. As NK‐cell inhibitory receptors play a role in bone marrow cell rejection, these same inhibitory receptors may also affect NK responses towards tumor cells. It has been demonstrated that blocking the interaction of inhibitory receptors with MHC determinants on tumor cells can result in greater antitumor effects. Thus, NK cells are capable of mediating both positive and negative effects during BMT depending on whether they are of host versus donor origin and their state of activation. Understanding their role in BMT provides insights as to their physiological roles and points the way to potential clinical uses. The authors are grateful for the excellent secretarial assistance by Ms Laura Knott. The authors thank Dr Lisbeth Welniak for critically reviewing the manuscript. WJM is particularly grateful to the members of his laboratory for contributing to the projects over the years and to his two mentors, MB and DLL, for their training and guidance, which allowed him to develop his studies on the basic and preclinical aspects of NK cells in BMT in his laboratory. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01‐CO‐56000, and by NIH grants CA36922, CA70134, and AI38938. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

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