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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3949-3959
Engraftment of Severe Combined Immune Deficient Mice Receiving
Allogeneic Bone Marrow Via In Utero or Postnatal Transfer
Bruce R. Blazar,
Patricia A. Taylor,
Ron McElmurry,
Lina Tian,
Angela Panoskaltsis-Mortari,
Sylvia Lam,
Chris Lees,
Thomas Waldschmidt, and
Daniel A. Vallera
From the University of Minnesota Cancer Center and Department of
Pediatrics, Division of Bone Marrow Transplantation and Pediatric
Oncology, Therapeutic Radiology, University of Minnesota, Minneapolis,
MN; and the Department of Pathology, University of Iowa, Iowa City, IA.
Although in utero transplantation (IUT) has been shown to be
effective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared with
postnatal bone marrow transplantation (BMT) for SCID is unknown.
Therefore, comparative studies were undertaken in mice to determine the
engraftment outcome in these two settings. Because T-cell depletion
(TCD) reduces graft-versus-host disease (GVHD) severity but compromises
alloengraftment, studies were performed with TCD or non-TCD BM and GVHD
risk was assessed using a tissue scoring system and by the adoptive
transfer 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 had
higher levels of donor T-cell and myeloid peripheral blood (PB)
engraftment than nonconditioned SCID recipients. Increased TCD or
non-TCD BM cell numbers in adult SCID recipients resulted in similar
levels of PB engraftment as IUT recipients. However, under these
conditions, mean GVHD scores were higher than in IUT recipients. The
majority of adoptive transfer recipients of splenocytes from IUT
recipients were GVHD-free, consistent with the in vitro evidence of
tolerance to host alloantigens. Total body irradiation (TBI)-treated
mice that had the highest engraftment had evidence of thymic damage as
denoted by a higher proportion of thymic and splenic T cells with a
memory phenotype as compared with IUT recipients. IUT mice had vigorous
thymic reconstitution by 3 weeks of age. Our data indicate that IUT has
a number of advantages as compared with postnatal BMT. Future studies
examining the fine specificity of immunoreconstitution in IUT versus
postnatal BMT are indicated.
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