NK cells in the regulation of hematopoiesis

Natural killer (NK) cells have long been thought to play a role in the regulation of hematopoiesis. In addition to their ability to lyse certain transformed cells in a MHC unrestricted manner, NK cells also reject bone marrow allografts but not solid tissue allografts in mice. Because NK cells are able to detect specific but poorly defined determinants present on hematopoietic cells, it was postulated that NK cells function in the homeostatic regulation of hematopoiesis. However, the precise nature of this regulation was unclear because there have often been confusing and contradictory reports concerning whether NK cells promote or inhibit syngeneic hematopoietic growth. The recent characterization of NK cell subsets offers a means to reconcile the previous literature, which used whole populations of NK cells or performed in vivo depletion of all NK cells using pan NK-specific markers. This review will present an overview of the previous literature concerning the role of NK cells in hematopoiesis, examine the assays used to study NK cell-hematopoietic cell interactions, provide evidence that NK cell subsets exert diverse effects on hematopoiesis depending on their MHC haplotype, and speculate on potential clinical applications of NK cells to promote hematopoiesis.