Experimental manipulations and marrow-derived factors which affect the outcome of bone marrow transplantation across the H-2 barrier in lethally irradiated mice

Abstract

A system is illustrated here for transplantation of bone marrow (BMT) across the H-2 barrier in conventionally raised mice. Timing of BM inoculation after supralethal irradiation, alteration of cellular composition of BM cell inoculum, sex of donor and recipient, inoculation or removal of BM-derived supernatants, use of BM-derived factors were all variables which profoundly affected survival, hemopoietic engraftment and induction of permanent, irreversible chimerism in different strains of mice (H-2d, H-2b, H-2k) transplanted with allogeneic BM. Inoculation of BM shortly after irradiation and addition or removal of plastic-adherent cells to the BM adversely affected survival and chimerism. Also inoculation of BM in its original supernatant containing all extracellular, endogenous BM factors resulted in increased mortality. BM-derived regulating factors (MRF) exerted variable effects in different H-2 combinations. However, heat-stable components of MRF greatly affected survival and chimerism. BM-derived supernatants and MRF from rabbit or different murine H-2 types thus seem to contain powerful inhibitors and promoters of BM engraftment. Promoters stimulate allogeneic BM engraftment, are heat-resistant and non-species specific. The different character and concentration of those factors between different H-2 types is also illustrated by their in vitro effects on BM cells. These results demonstrate that different experimental manipulations and factors which do not strictly depend on genetic diversity between donor and recipient profoundly affect allogeneic BMT. Adoption of manipulations combined with use of non-T cell depleted BM and the still largely unidentified BM-derived factors result in increment of survival and lasting chimerism without any manifestation of early or late graft versus-host disease (GVHD).