Autologous graft-versus-host disease in a porcine bone marrow transplant model

BACKGROUND: Autologous graft-versus-host disease (autoGvHD) has been reported in patients and can be induced in rodents by syngeneic bone marrow transplantation (BMT) and a brief administration of cyclosporine A (CsA). To our knowledge, there is no previous large-animal model for this phenomenon, nor is there a model in which autoGvHD occurs spontaneously after autologous bone marrow transplant (autoBMT) in the absence of CsA induction. During our studies of autoBMT in miniature swine, performed without CsA treatment, we noted the frequent occurrence of a rash consistent with autoGvHD. We hypothesized that the extent of peripheral blood contamination of the bone marrow (BM) inoculum before transplant may have correlated with the incidence of such autoGvHD. METHODS: Retrospective analysis of the prevalence of autoGvHD in swine was carried out in all animals that had become engrafted after autoBMT in our laboratory. Subsequent prospective experiments attempted to induce autoGvHD by transplanting autologous BM enriched with autologous peripheral blood into lethally irradiated animals. RESULTS: Our data showed that autoGvHD frequently occurs in swine after autoBMT, with the most severe cases of the disease occurring in animals with the highest levels of peripheral blood contamination of the BM inoculum. Furthermore, mixed lymphocyte reactions (MLR) against self antigens were positive only in animals affected by autoGvHD. CONCLUSION: These findings provide the first evidence for autoGvHD without the use of CsA in a preclinical BMT model. The role of autologous T cells needs further delineation but may help to explain the occasional occurrences of autoGvHD that have been reported in humans after autoBMT.