Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation

Sabrina M Scroggins; Alicia K Olivier; David K Meyerholz; Annette J Schlueter

doi:10.1371/journal.pone.0075158

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Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation

Journal article

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Peer reviewed

Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation

Sabrina M Scroggins, Alicia K Olivier, David K Meyerholz and Annette J Schlueter

PloS one, Vol.8(9), pp.e75158-e75158

2013

DOI: 10.1371/journal.pone.0075158

PMCID: PMC3769303

PMID: 24040397

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Abstract

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC may utilize to induce and maintain tolerance to GVHD.

Acute Disease

Gene Expression Regulation - immunology

Dendritic Cells - immunology

Humans

Immune Tolerance

Adoptive Transfer

Graft vs Host Disease - metabolism

Graft vs Host Disease - immunology

Aging - immunology

B7-H1 Antigen - metabolism

Phenotype

Animals

Aging - physiology

Time Factors

Graft vs Host Disease - physiopathology

Bone Marrow Transplantation - adverse effects

Mice

Graft vs Host Disease - etiology

Cytokines - biosynthesis

Receptors, Immunologic - metabolism

Transplantation, Homologous - adverse effects

Details

Title: Subtitle: Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation
Creators: Sabrina M Scroggins - Interdisciplinary Graduate Program in Immunology, University of Iowa Graduate College, Iowa City, Iowa, United States of America ; Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa, United States of America
Alicia K Olivier
David K Meyerholz
Annette J Schlueter
Resource Type: Journal article
Publication Details: PloS one, Vol.8(9), pp.e75158-e75158
DOI: 10.1371/journal.pone.0075158
PMID: 24040397
PMCID: PMC3769303
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: 5T32AI007485 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS
Language: English
Date published: 2013
Academic Unit: Pathology; Obstetrics and Gynecology
Record Identifier: 9984047735102771

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