Allogeneic intra-BM-BMT plus adult thymus transplantation from same donor has benefits for long-term survival even after sublethal irradiation or low-dose BM cell injection

Abstract

We examined the effects of intra-BM-BMT (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor after 5.5 Gy sublethal irradiation (SubLI) or low-dose (3 x 10(6)) BM cell injection (LDBMCI). With SubLI, BALB/c mice that had received 1 x 10(7) bone marrow cells by IBM-BMT plus ATT from B6 mice showed 73% donor chimerism, whereas those treated with IBM-BMT alone showed 45% chimerism. In the LDBMCI with 7Gy irradiation, IBM-BMT plus ATT resulted in a 90% survival rate with 90% chimerism, whereas IBM-BMT alone resulted in a 55% survival rate with 44% chimerism. Although the number of CD4 T cells was higher in IBM-BMT plus ATT than in IBM-BMT alone, the percentages of FoxP3+/CD4+ T cells and lymphocyte functions in the former were almost identical to those in the latter. When treated with IBM-BMT plus donor lymphocyte infusion (DLI), the mice showed a reduced survival time as a result of GVHD, with low numbers of FoxP3+CD4 T cells under either condition, although 100% chimerism was induced. These results suggest that IBM-BMT plus ATT is effective in reconstituting the recipients with donor-derived cells even after SubLI or LDBMCI.