Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice

Dapeng Wang, Yu Yu, Kelley Haarberg, Jianing Fu, Kane Kaosaard, Srinivas Nagaraj, Claudio Anasetti, Dmitry Gabrilovich, Xue Zhong Yu

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of myeloid cells composed of hematopoietic progenitor cells, immature macrophages, dendritic cells, and granulocytes, which accumulate in inflammatory diseases and various cancers. Here, we investigated the dynamic changes and effects of MDSCs in graft-versus-host disease (GVHD) development and/or tumor relapse after syngeneic and allogeneic bone marrow transplantation (BMT). We found that adding functional MDSCs in donor graft alleviated GVHD, whereas removal of MDSCs in vivo exacerbated GVHD. After T cell-deplete BMT, MDSCs transiently accumulated in the blood and spleen of recipients without GVHD. In contrast, after T cell-replete BMT, the levels of blood MDSCs were constantly elevated in recipients with GVHD. MDSC accumulation positively correlated with the severity of GVHD. Additionally, MDSC accumulation was further increased upon tumor relapse. Although MDSCs isolated from both syngeneic and allogeneic BMT recipients inhibited T cell proliferation in response to alloantigen stimulation ex vivo, MDSCs from the recipients with GVHD showed much higher suppressive potency compared with those from recipients without GVHD. These results indicate that MDSCs can regulate the immune response in acute GVHD, and possibly tumor relapse, subsequent to allogeneic BMT.

Original languageEnglish (US)
Pages (from-to)692-702
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

Keywords

  • BMT
  • GVHD
  • MDSC
  • Tumor relapse

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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