The Possible Role of the Id-network in the Development of Late Onset Graft-versus-host Disease after Bone Marrow Transplantation: Importance of the Microflora of the Bone Marrow Recipient

One of the major complications of allogeneic bone marrow transplantation (BMT) is graft-versus-host disease (GvHD), which is caused by donor type lymphocytes which react against the recipient’s tissues. An important factor which influences GvHD is the recipient's gastrointestinal microflora. This was originally observed in gnotobiotic mice. Infusion of 107 H-2 incompatible bone marrow cells into lethally irradiated (9.0 Gy X-rays) conventional mice results in a late onset type GvHD which causes the death of the majority of the recipients during the first two months after BMT. This mortality can be completely prevented if the recipients are germfree mice, or when they are conventional animals which have been subjected to complete gastrointestinal decontamination. Donor ( C57Bl/Rij) and recipient (C3H/Law) mice with different defined microfloras were obtained by using offspring from germfree C3H/Law mothers that were contaminated with the different floras or by using those C3H/Law females to foster hysterectomy-derived C57Bl/Rij new-borns. Studies using these donor and recipient mice resulted in significantly different mortality rates due to GvHD. This observation can be explained by the hypothesis that during gestation and fostering, the developing immune system of new-born animals is modulated by the "experienced" immune system of the dam, resulting in immunological tolerance to flora-components of the (foster-) mothers.