Effect of selective decontamination of the digestive tract of donor and recipient on the occurrence of murine delayed-type graft-versus-host disease.

In the present study we investigated the occurrence of delayed-type graft-versus-host disease (DT-GvHD) after allogeneic bone marrow transplantation (BMT) between two H-2 incompatible mouse strains. BMT was performed on mice with a conventional intestinal microflora as well as on mice in which the Enterobacteriaceae were selectively eliminated from the intestinal microflora by oral antibiotic treatment. None of the conventional or the selectively decontaminated (SD) chimaeric mice suffering from DT-GvHD died of bacteraemia. While DT-GvHD was mitigated when C3H/He recipient mice were SD-treated, this was not the case when C57B1/6J recipient mice were SD-treated. SD-treatment of the digestive tract of donor mice only mitigated DT-GvHD when the recipients were also SD-treated. We conclude that Enterobacteriaceae in the digestive tract may only play a minor role, if any, in the occurrence of DT-GvHD. Instead, we postulate that in this study DT-GvHD was determined by differences in the composition of the resident intestinal microflora (IM) of both mouse strains together with the cellular composition of the bone marrow graft. The interaction between antigenic components of the recipient's IM and the developing donor immune system in the recipient as a possible cause for DT-GvHD is discussed.