Transplantation of newborn thymus plus hematopoietic stem cells can rescue supralethally irradiated mice.

ABSTRACT

We attempted to rescue supralethally irradiated (SLI) mice by transplantation of hematopoietic stem cells (HSCs) plus thymus from variously aged donors (fetus, newborn and adult). Although the transplantations of these kinds of HSCs alone showed a very short survival, newborn liver cells (NLCs) (as the source of HSCs) plus newborn thymus (NT) transplantation markedly improved the survival rate. The transplantation attenuated severe damage in the small intestine, which is one of the major causes of death by SLI. In addition, the donor-derived CD4(+) T cells significantly increased with additional NT transplantation. The production of interleukin (IL)-7 and keratinocyte growth factor, which plays a crucial role in protection against radiation injury in the intestine, was the highest in NT. Finally, SLI mice that had received NLC plus IL-7(-/-) NT transplantation plus IL-7 injection showed improved survival, weight recovery and an elevated number of CD4(+) T cells compared with the mice that had received NLC plus IL-7(-/-) NT or plus IL-7 injection alone. These findings suggest that NLCs plus NT transplantation can rescue SLI mice most effectively, and that high production of IL-7 in NT plays a crucial role with induction of CD4(+) T cells.