Induction of Unresponsiveness to Bone Marrow Grafts

Abstract Unresponsiveness to Hh incompatible bone marrow grafts was induced in mice by single or multiple injections of various tissues from a prospective donor before irradiation and bone marrow grafting. The results show that lymph node cells and splenocytes (both adherent and nonadherent) were the most effective in inducing unresponsiveness; thymocytes showed only a marginal effect in female and no effect in male mice, and hepatocytes had no effect. There was a direct relationship between the number of cells required for unresponsiveness induction and the strength of incompatibility between donor and recipient, i.e., the stronger the donor-recipient incompatibility, the more cells were required to induce unresponsiveness. The rapidity of unresponsiveness induction and its duration were also dependent on the number of cells in the “immunizing” inoculum. In general, unresponsiveness was induced sooner and persisted longer when larger cell doses were used. The unresponsiveness was highly specific with regard to donor antigens.</jats:p

Abrogation of Resistance to Bone Marrow Grafts by Silica Particles

Abstract An attempt was made to assess the role of macrophages in resistance of irradiated mice to parental-strain and allogeneic bone marrow grafts. 1.25 to 5 mg of silica particles injected i.v. (5 µ average size) are specifically toxic to macrophages and resulted in prompt abrogation or reduction of hybrid and allogeneic resistance. The silica was equally effective when given within 2 days before or after transplantation of bone marrow cells. The effectiveness decreased with increasing intervals, but foreign marrow cells could be rescued from rejection as long as 3 days after grafting. The macrophage stabilizer poly-2-vinylpyridine N-oxide injected subcutaneously (150 mg/kg) 1 day before silica entirely prevented the suppression of hybrid resistance. It was concluded that macrophages, or a subpopulation thereof, could be the effectors of hemopoietic graft rejection by irradiated mice. The immunogenetic specificity of these allograft reactions and the suppressive effects of anti-lymphocyte agents suggest, however, that also lymphoid cells participate in this process.</jats:p

Resistance of Irradiated F1 Hybrid and Allogeneic Mice to Bone Marrow Grafts of NZB Donors

Abstract Heavily irradiated mice of several inbred and F1 hybrid strains were classified as resistant or susceptible to allogeneic or parental grafts of 106 NZB bone marrow cells depending on the 5-day hemopoietic repopulation of host spleens. Several strains did not support the growth of donor cells despite the total-body irradiation. NZW × NZB F1 mice resisted the growth of as many as 4 × 107 parental cells, the strongest barrier ever observed in mice for marrow transplants. The failures of growth were due to host-anti-graft reactions depressible by pretreatment of recipients with cyclophosphamide or horse anti-mouse thymocyte serum. Analysis of the progeny of two separate backcrosses of F1 mice to NZB indicated that two non-linked autosomal genes controlled resistance. One of these genes was in linkage group IX, 31.42 crossing-over units away from the D end of H-2, specifying or controlling the expression of alloantigen-like components of hemopoietic cells (Hh-gene). The second gene had an epistatic effect, probably by regulating the recognition of, or the reactivity to, Hh-gene products.</jats:p