Prolonged skin allograft survival in Scid mice reconstituted with isogeneic bone marrow stem cell antigen-1-positive cells and thymus tissue.

INTRODUCTION

Many studies indicate that tolerance induction is much more dependent on the maturation status of lymphocytes than the age of the animal. We hypothesized that direct persistent contact of bone marrow stem cells with graft alloantigen will result in tolerance to that antigen in the adult animal.

MATERIAL AND

METHODS

Severe combined immunodeficient mice (CB-17-Scid, H-2b) were reconstituted with isogeneic bone marrow stem cell antigen-1 (Sca-1)-positive cells and grafted with fetal thymus (BMSC-T), followed by transplant of allogeneic skin grafts from C57BL/6 (H-2d) mice. The control group include CB-17 non-Scid mice, CB-17-Scid mice, and CB-17 Scid mice pretransplanted with nonmodified isogeneic bone marrow cells and fetal thymus (BMC-T).

RESULTS AND DISCUSSION: Skin allograft survival was significantly prolonged in the group pretransplanted with isogeneic BMSC-T compared the group of non-Scid mice and the group of Scid mice pretransplanted with BMC-T (59.6 days vs 7.1 days vs 11.7 days). In 2 of 10 mice pretransplanted with BMSC-T, the skin allografts transplanted immediately after BMSC-T survived for more than 100 days, but the third-party skin allografts transplanted at 100 days after BMSC-T transplant were rejected. The results suggest direct persistent contact of bone marrow Sca-1-positive cells with graft alloantigen may be a feasible approach to prolong allograft survival and induce tolerance in a small fraction of adult animals.