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 presenting cells (APC) which survive the transplant conditioning regimen. We examined whether the depletion of hepatic and splenic APC could reduce the severity of hepatic GVHD after bone marrow transplantation (BMT).


METHODS
Recipient mice were depleted for hepatic and splenic phagocytic APCs by i.v. injection of clodronate- (dichloromethylene diphosphonate) containing 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-depleted mice and control mice. APC-depleted mice had increased peritransplant mortality due to sepsis. Bacterial clearance assays showed that APC-depleted mice were unable to efficiently clear bacteria, although nondepleted, transplanted mice were able to clear bacteria as quickly as naive control mice.


CONCLUSIONS
Residual host phagocytic APC do not appear to play a role in the induction of GVHD after BMT. They are, however, essential for prevention of sepsis in the transplant host.
Everse
L A
LA
Department of Pediatrics, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Anderson
L D
LD
van Rooijen
N
N
Mullen
C A
CA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000187:drug effects*; D001770:Blood Bactericidal Activity / Q000187:drug effects; D001781:Blood Component Removal / Q000379:methods*; D016026:Bone Marrow Transplantation / Q000401:mortality*; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000503:physiopathology*; D006648:Histocompatibility; D007275:Injections, Intravenous; D008081:Liposomes; D051379:Mice; D008815:Mice, Inbred Strains; D012016:Reference Values; D012720:Severity of Illness Index; D014118:Toxins, Biological / Q000494:pharmacology; D019172:Transplantation Conditioning
D008081:Liposomes; D014118:Toxins, Biological; D004002:Clodronic Acid