Reconstitution of BIO recipient mice, conditioned with total body irradiation (950 rads), with 40x106 untreated F344 or WF rat bone marrow cells results in stable rat stem-cell engraftment with multilineage lym-phohematopoietic chimerism. We have now characterized NK cell generation, maturation, and function in fully xenogeneic chimeras (WF rat → BIO mouse; F344 → BIO mouse). Early during xenogeneic reconstitution, rat-derived NK cells predominated in splenic lymphoid tissue, composing 14-18% of total cells at week 1 and increasing to 35.6-59.9% of total cells at week 2. By week 6, levels of rat NK cells had decreased and stabilized to that expected for normal rat (9-14.2%). The NK chimerism was reliably stable for up to 7 months following reconstitution. Most importantly, rat-derived NK cells were functional in both YAC tumor cytolysis and ADCC assays, suggesting that the xenogeneic mouse host environment was sufficient to support the generation, maturation, and function of rat-derived NK cells.
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