In utero hematopoietic stem cell transplantation (IUT) results in limited chimerism and tolerance to alloantigens. We studied the relative role of @entity24653 expression by dendritic cells (DCs) in engraftment and in generating donor-specific tolerance in fetal @entity19 . Mature dendritic cells (mDCs) from @entity8271 (-/-) or @entity11787 (-/-) donors and wild-type (WT) lineage-depleted ( @entity54854 ) C57BL/6 (B6) bone marrow (BM) were injected into BALB/c fetuses. Six weeks after IUT, @entity8271 (-/-) recipients had multilineage engraftment (4.7% +/- 0.8% T cells and 5.7% +/- 1.1% granulocytes) associated with @entity2132 ( @entity2132 ) and decreased survival, but by 12 weeks only donor @entity5168 (+) cells (2.1% +/- 1.3%) were present. Recipients of @entity11787 (-/-) mDCs and lin(-) WT B6 BM had exclusively @entity5168 (+) @entity1961 (+) T cells (11.8% +/- 8.5% at 6 weeks and 6.5% +/- 2.5% at 12 weeks). Most of the cells were T-helper 2, although 10.4% +/- 1.4% were of the T-regulatory (T(reg)) phenotype, ie, @entity1961 (+)CD25(+). Donor T(reg) cells were detected both in the thymus and spleen, thus suggesting an effect on both central and peripheral immunity. The animals with T(reg) cells had better survival (82.3% versus 47.4%; P < .01) and no @entity2132 (0% versus 65%; P < .001). This group alone demonstrated multilineage engraftment of donor hematopoietic cells after postnatal transplantation with megadoses of donor @entity54854 BM. Both the engrafted donor @entity1961 (+)CD25(-) and @entity1961 (+)CD25(+) cells induced comparable in vitro suppression of T-cell proliferation, thus suggesting their role in the persistence of the donor T cells in vivo. The @entity1961 (+)CD25(-) cells produced @entity1618 or @entity58 and were inhibited by anti-T-helper 2 cytokine-neutralizing antibodies, whereas the @entity1961 (+)CD25(+) cells showed no evidence of any involvement of a cytokine-like soluble mediator and expressed @entity17796 ( @entity17796 ) and @entity3744 constitutively. Donor mDCs and donor @entity1961 T cells were detected among the thymocytes of the recipients of @entity11787 (-/-) mDCs and lin(-) WT B6 BM. Thus, it seems that costimulatory molecule expression of donor DCs can play a significant immunomodulatory role in survival, @entity2132 , engraftment, and homing of allogeneic BM cells after IUT through the generation of T(reg) cells.

@entity11787 -/- mature dendritic cells generate T-helper 2 and regulatory T donor cells in fetal XXXX after in utero allogeneic bone marrow transplantation.

@entity19 :: ('10090', 'Species') :: ['mice'] @entity8271 :: ('12519(Tax:10090)', 'Gene') :: ['B7.1'] @entity17796 :: ('12477(Tax:10090)', 'Gene') :: ['CTLA-4', 'cytotoxic T-lymphocyte antigen 4'] @entity5168 :: ('12501(Tax:10090)', 'Gene') :: ['CD3'] @entity54854 :: ('CHEBI:32386', 'Chemical') :: ['lin(-)'] @entity1618 :: ('16153(Tax:10090)', 'Gene') :: ['interleukin 10'] @entity11787 :: ('12524(Tax:10090)', 'Gene') :: ['B7.2'] @entity1961 :: ('12504(Tax:10090)', 'Gene') :: ['CD4'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['GVHD', 'graft-versus-host disease'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['interleukin 4'] @entity24653 :: ('12519;12524', 'Gene') :: ['B7.1 and B7.2'] @entity3744 :: ('20371(Tax:10090)', 'Gene') :: ['foxp3']
@entity19 :: (10090,Species) :: ['mice']
