ENGRAFTMENT OF DISCORDANT XENOGENEIC SWINE BONE-MARROW CELLS IN IMMUNODEFICIENT MICE

We have recently demonstrated that swine bone marrow cells (BMC) can e ngraft in C.B-17 scid mice. While engraftment is enhanced by providing donor-specific porcine cytokines, the level of swine hematopoiesis de clines between 3 and 6 weeks post-transplant. In the present study, th e utility of several strains of immunodeficient mice as recipients of swine hematopoietic cells has been determined by comparing levels of s wine bone marrow engraftment at 3 weeks after bone marrow transplant. Irradiated recipients were injected with 1x10(8) swine BMC and were tr eated daily with porcine cytokines. The presence of swine cells in BMT recipients was detected by flow cytometry and marrow colony-forming a ssays. Recombination activating gene-1 (RAG-l)-deficient mice were not permissive for the engraftment of swine BMC, even with administration of increased doses of whole body irradiation, or with depleting anti- NK cell antibody. In contrast, NOD-scid mice showed improved swine BMC engraftment compared to C.B-17 scid mice. Levels of swine class I+, m yeloid, and CD2(+) cells in bone marrow, spleen, and peripheral blood, and the number of porcine myeloid progenitor cells was significantly higher in NOD-scid recipients than in simultaneous C.B-17 scid recipie nts, In addition, the sera from C.B-17 scid mice markedly inhibited th e proliferation of swine BMC in vitro., A weaker inhibitory effect was also mediated by sera from RAG-1-deficient! mice, but not by sera fro m NOD-scid mice. Together, our results indicate that multiple host ele ments resist xenogeneic hematopoietic engraftment and function, some o f which are clearly independent of host T, B, or NK cells. Understandi ng the basis for the advantage of NOD-scid mice as recipients of disco rdant xenogeneic porcine BMC will help to identify these elements.