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

Linda A. Everse, Larry D. Anderson, Nico Van Rooijen, Craig A. Mullen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 naïve 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.

Original languageEnglish (US)
Pages (from-to)611-618
Number of pages8
JournalTransplantation
Volume71
Issue number5
StatePublished - Mar 15 2001

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Clodronic Acid
Graft vs Host Disease
Antigen-Presenting Cells
Bone Marrow Transplantation
Bone Marrow
Transplants
Mortality
Liver
Sepsis
Bacteria
Phagocytes
Liposomes
T-Lymphocytes
Injections

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Bone marrow transplant conditioning intensified with liposomal clodronate to eliminate residual host antigen presenting cells fails to ameliorate GVHD and increases peri-BMT mortality. / Everse, Linda A.; Anderson, Larry D.; Van Rooijen, Nico; Mullen, Craig A.

In: Transplantation, Vol. 71, No. 5, 15.03.2001, p. 611-618.

Research output: Contribution to journalArticle

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abstract = "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 na{\"i}ve 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.",
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N2 - 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 naïve 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.

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