ACTIVATED NATURAL KILLER CELLS AND INTERLEUKIN-2 PROMOTE GRANULOCYTIC AND MEGAKARYOCYTIC RECONSTITUTION AFTER SYNGENEIC BONE MARROW TRANSPLANTATION

Abstract

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells (SC) were cultured and activated with recombinant human interleukin-2 rhIL-2) in vitro. This gave rise to pure populations of activated NK cells. The activated NK cells were then transferred with bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on hematopoietic reconstitution. On analysis, the transfer of rhIL-2-activated NK cells along with BMC resulted in significant increases in splenic and bone marrow hematopoietic progenitor cells when compared to mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC's showed a marked increase in survival rate. These results demonstrate that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL-2 may be of clinical use to promote hematopoietic reconstitution after BMT.