In utero transfer of adult bone marrow cells into recipients with severe combined immunodeficiency disorder yields lymphoid progeny with T- and B-cell functional capabilities

Abstract

To determine if in utero transplantation could restore the immune system of mice with a severe combined immunodeficiency (SCID) disorder, C57BL/6Sz-scid/scid fetuses were injected on day 14/15 of gestation with adult congenic donor bone marrow (BM) cells. Congenic BM engrafted in one of eight (13%) recipients. Reconstitution of both lymphoid and nonlymphoid lineages was observed. In vitro and in vivo T-cell function was documented. Stem cells were shown to have engrafted by secondary transfer studies. When fully allogeneic C57BL/6 (H-2b) or B10.BR (H-2k) adult. BM cells were given to C.B-17-scid/scid (H-2d) fetal recipients, 15 of 54 (28%) recipients had evidence of engraftment, with up to 76% of peripheral blood (PB) being of in utero donor BM origin on day 131 postnatally. In all mice with persistent leukocyte engraftment, T- and B-lymphoid cells were entirely of donor origin. Donor T cells were tolerant to host but not third party alloantigens as measured in vitro. In vivo, T-cell function appeared intact. Although most mice had lower levels of B-cell engraftment than T-cell engraftment, mice with > or = 10% B cells were able to produce normal levels of IgM. Despite transplantation of fully allogeneic BM cells, stem cell engraftment could be demonstrated by secondary transfer of BM cells into lethally irradiated recipients that were congenic to the original in utero donor BM source. These data indicate that adult BM cells, even those fully allogeneic with the fetal recipient, can give rise to progeny with multilineage potential, which leads to restoration of T-cell and B-cell function.