BONE MARROW TRANSPLANTATION ACROSS MAJOR HISTOCOMPATIBILITY BARRIERS IN MICE

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Abstract
The role of T lymphocytes in engraftment of bone marrow (BM) was examined in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-vs.-host disease(GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment .apprx. 1 mo. after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 .times. 100 rad TLI. In TLI plus Cy-conditioned recipients, increasing the donation of treated bone marrow cells still did not result in significant engraftment. Graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Removal of BM T cells with monoclonal anti-Lyt-1 plus C also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed.

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