INUTERO TRANSPLANTATION OF HEMATOPOIETIC STEM-CELLS IN SHEEP - THE ROLE OF T-CELLS IN ENGRAFTMENT AND GRAFT-VERSUS-HOST DISEASE

Transplantation of hematopoietic stem cells (HSC) from adult sheep into fetal lambs results in hematopoietic chimerism and graft-versus-host disease (GVHD). To evaluate the role of T cells in HSC engraftment and GVHD we depleted adult marrow HSC of T cells and observed the incidence of chimerism and GVHD in the fetal recipients. Using a naturally occuring polymorphism of the β-globin locus to detect engraftment, bone marrow obtained from homozygous type A hemoglobin adult sheep were transplanted (2 × 109 cells/kg fetal weight) into 90 days' gestation fetal lambs homozygous for type B hemoglobin. Donor HSC were T-cell depleted by treatment with antisera (raised in rabbits against sheep thymocytes) in the presence of complement. T-cell depletion resulted in significant decrease in hematopoietic colony formation by donor HSC in vitro (305 ± 49 v 134 ± 21 colonies/105 cells) that normalized by the addition of autologous T cells (433 ± 32 colonies/105 cells). Marrow depleted of T cells exhibited reduced engraftment in the recipient fetuses. When T cells were added back to donor HSC (depleted of T cells) at near-normal concentrations, engraftment improved but the lambs also developed GVHD. The addition of T cells to donor HSC (depleted of T cells) at concentrations below that present in unprocessed bone marrow resulted in significant engraftment but not GVHD. T cells play an important role in both the engraftment of adult HSC in fetal recipients and the development of GVHD in chimeric newborns. The elimination of T cells prevents GVHD but markedly reduces engraftment. By the reduction, but not elimination, of T cell number, it is possible to preserve the ability of adult HSC to engraft in the fetus without the development of GVHD. © 1990.