Bone marrow transplant conditioning intensified with liposomal clodronate to eliminate residual host antigen presenting cells fails to ameliorate GVHD and increases peri-BMT mortality

Background Graft versus host disease (GVHD) mediated by allogeneic donor T cells may be initiated and/or exacerbated by residual host antigen presenti ng cells (APC) which survive the transplant conditioning regimen, We examin ed whether the depletion of hepatic and splenic APC could reduce the severi ty of hepatic GVHD after bone marrow transplantation (BMT). Methods. Recipient mice were depleted for hepatic and splenic phagocytic AP Cs by i,v, injection of clodronate- (dichloromethylene diphosphonate) conta ining liposomes before fully allogeneic or MHC-matched, minor Ag-mismatched BMT, Severity of hepatic GVHD was scored on histological sections 2, 3, 4, or 9 weeks after BMT, Results, No differences in the severity of GVHD were observed between APC-d epleted mice and control mice. APC-depleted mice had increased peritranspla nt mortality due to sepsis, Bacterial clearance assays showed that APC-depl eted mice were unable to efficiently clear bacteria, although nondepleted, transplanted mice were able to clear bacteria as quickly as naive control m ice. Conclusions. Residual host phagocytic APC do not appear to play a role in t he induction of GVHD after BMT. They are, however, essential for prevention of sepsis in the transplant host.