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The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.

Graft-versus-host disease (GVHD) is a major barrier to the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating hematologic malignancies. Myeloid-derived suppressor cells (MDSCs) have been recognized as crucial immunosuppressive cells in various pathologic se...

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Autores principales: Zhang, Jilu, Chen, Hui-Ming, Ma, Ge, Zhou, Zuping, Raulet, David, Rivera, Andreana L., Chen, Shu-Hsia, Pan, Ping-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687551/
https://www.ncbi.nlm.nih.gov/pubmed/30737483
http://dx.doi.org/10.1038/s41375-019-0394-z
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author Zhang, Jilu
Chen, Hui-Ming
Ma, Ge
Zhou, Zuping
Raulet, David
Rivera, Andreana L.
Chen, Shu-Hsia
Pan, Ping-Ying
author_facet Zhang, Jilu
Chen, Hui-Ming
Ma, Ge
Zhou, Zuping
Raulet, David
Rivera, Andreana L.
Chen, Shu-Hsia
Pan, Ping-Ying
author_sort Zhang, Jilu
collection PubMed
description Graft-versus-host disease (GVHD) is a major barrier to the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating hematologic malignancies. Myeloid-derived suppressor cells (MDSCs) have been recognized as crucial immunosuppressive cells in various pathologic settings. Here, we investigated whether the unique functional properties of MDSCs could be harnessed to control allo-HSCT-associated GVHD. Using multiple murine GVHD/GVL models including both MHC-mismatched and miHA-mismatched, we demonstrated that treatment with CD115+ MDSCs efficiently suppressed GVHD but did not significantly impair graft-versus-leukemia (GVL) activity, leading to 80% and 67% protection in treated mice in GVHD and GVL models, respectively. The mechanism for this dissociation of GVHD from GVL, specifically the emergence of donor-derived NKG2D(+) CD8 T cells with a memory phenotype in MDSC-treated recipient mice, was identified. NKG2D expression on donor T cells was required for eradication of allogeneic lymphoma cells. Furthermore, long-term surviving MDSC recipients that exhibited cytolytic activities against allogeneic leukemia cells had a significantly increased percentage of T regulatory cells and, more importantly, NKG2D(+) CD8 T cells. These findings indicate that MDSCs can be used as a novel cell-based therapy to suppress GVHD while maintaining GVL activities through selective induction of NKG2D(+) CD8 memory T cells.
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spelling pubmed-66875512019-08-09 The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells. Zhang, Jilu Chen, Hui-Ming Ma, Ge Zhou, Zuping Raulet, David Rivera, Andreana L. Chen, Shu-Hsia Pan, Ping-Ying Leukemia Article Graft-versus-host disease (GVHD) is a major barrier to the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating hematologic malignancies. Myeloid-derived suppressor cells (MDSCs) have been recognized as crucial immunosuppressive cells in various pathologic settings. Here, we investigated whether the unique functional properties of MDSCs could be harnessed to control allo-HSCT-associated GVHD. Using multiple murine GVHD/GVL models including both MHC-mismatched and miHA-mismatched, we demonstrated that treatment with CD115+ MDSCs efficiently suppressed GVHD but did not significantly impair graft-versus-leukemia (GVL) activity, leading to 80% and 67% protection in treated mice in GVHD and GVL models, respectively. The mechanism for this dissociation of GVHD from GVL, specifically the emergence of donor-derived NKG2D(+) CD8 T cells with a memory phenotype in MDSC-treated recipient mice, was identified. NKG2D expression on donor T cells was required for eradication of allogeneic lymphoma cells. Furthermore, long-term surviving MDSC recipients that exhibited cytolytic activities against allogeneic leukemia cells had a significantly increased percentage of T regulatory cells and, more importantly, NKG2D(+) CD8 T cells. These findings indicate that MDSCs can be used as a novel cell-based therapy to suppress GVHD while maintaining GVL activities through selective induction of NKG2D(+) CD8 memory T cells. 2019-02-08 2019-08 /pmc/articles/PMC6687551/ /pubmed/30737483 http://dx.doi.org/10.1038/s41375-019-0394-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zhang, Jilu
Chen, Hui-Ming
Ma, Ge
Zhou, Zuping
Raulet, David
Rivera, Andreana L.
Chen, Shu-Hsia
Pan, Ping-Ying
The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title_full The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title_fullStr The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title_full_unstemmed The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title_short The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.
title_sort mechanistic study behind suppression of gvhd while retaining gvl activities by myeloid-derived suppressor cells.
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687551/
https://www.ncbi.nlm.nih.gov/pubmed/30737483
http://dx.doi.org/10.1038/s41375-019-0394-z
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