Allogeneic bone marrow transplantation in conventional mice: I. Effect of antibiotic therapy on long term survival of allogeneic chimeras

Abstract

In the present communication the beneficial effect of long term antimicrobial treatment with poorly absorbable antiboitics on the survival of allogeneic bone marrow chimeras was investigated. The combination of C57Bl mice as bone marrow donors and CBA/CA mice as irradiated recipients (800 rad) was used because of their strong histoincompatibility on the H-2 loci. All allografted recipients received 10 X 10(6) bone marrow cells. The majority of the recipients, which were rendered gnotobiotic by an antimicrobial treatment, achieved stable long term chimerism. In contrast, the conventional chimeras died from secondary disease within 9 weeks after transplantation. As early as 14 days after allogeneic bone marrow grafting the gnotobiotic recipients tolerated the reassociation with a conventional microflora without a change in the rate of mortality. Bone marrow cells (8 X 10(6) i.v.) and spleen cells (2 X 10(6) i.v.) collected from allogeneic chimeras failed to induce graft-versus-host-reaction (GVH) in a second lethally irradiated host. The data indicate, that the high rate of mortality in murine allogeneic bone marrow chimeras results from delayed GVH-reaction and systemic infection. The marrow graft, once established seems to exert tolerance against the allogeneic host. The pathogenesis of the systemic infection has not yet been worked out. It is assumed that it originates from bacteremia, induced by radiation dependent lesions of the epithelial integrity and defected lymphatic tissue in the gut.