Engraftment of Severe Combined Immune Deficient Mice Receiving Allogeneic Bone Marrow Via In Utero or Postnatal Transfer

Although in utero transplantation (IUT) has been shown to beeffective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared withpostnatal bone marrow transplantation (BMT) for SCID is unknown.Therefore, comparative studies were undertaken in mice to determine theengraftment outcome in these two settings. Because T-cell depletion(TCD) reduces graft-versus-host disease (GVHD) severity but compromisesalloengraftment, studies were performed with TCD or non-TCD BM and GVHDrisk was assessed using a tissue scoring system and by the adoptivetransfer of splenocytes from engrafted mice into secondary recipients. Non-SCID recipients received pre-BMT irradiation to simulate those circumstances in which conditioning is required for alloengraftment. IUT recipients of non-TCD and especially TCD BM cells in general hadhigher levels of donor T-cell and myeloid peripheral blood (PB)engraftment than nonconditioned SCID recipients. Increased TCD ornon-TCD BM cell numbers in adult SCID recipients resulted in similarlevels of PB engraftment as IUT recipients. However, under theseconditions, mean GVHD scores were higher than in IUT recipients. Themajority of adoptive transfer recipients of splenocytes from IUTrecipients were GVHD-free, consistent with the in vitro evidence oftolerance to host alloantigens. Total body irradiation (TBI)-treatedmice that had the highest engraftment had evidence of thymic damage asdenoted by a higher proportion of thymic and splenic T cells with amemory phenotype as compared with IUT recipients. IUT mice had vigorousthymic reconstitution by 3 weeks of age. Our data indicate that IUT hasa number of advantages as compared with postnatal BMT. Future studiesexamining the fine specificity of immunoreconstitution in IUT versuspostnatal BMT are indicated.