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Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance

Graft versus host disease (GvHD) remains a limiting factor for successful hematopoietic stem cell transplantation (HSCT). T cells and antigen-presenting cells (APCs) are major components of the hematopoietic G-CSF mobilized peripheral blood cell (MPBC) graft. Here we show that a short incubation (2 ...

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Autores principales: Levy-Barazany, Hilit, Shachnai-Pinkas, Liat, Rodionov, Galina, Saar, Alex, Rosenzwaig, Michal, Gez, Liron, Rodin, Anastasia, Marelly, Nitzan, Abraham, Michal, Mishalian, Inbal, Wildbaum, Hila, Katz, Tamar, Baar, Yuval, Yarkoni, Shai, Bakimer-Kleiner, Ronit, Peled, Amnon, Zuckerman, Tsila, Stein, Jerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329633/
https://www.ncbi.nlm.nih.gov/pubmed/32433499
http://dx.doi.org/10.1038/s41409-020-0941-2
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author Levy-Barazany, Hilit
Shachnai-Pinkas, Liat
Rodionov, Galina
Saar, Alex
Rosenzwaig, Michal
Gez, Liron
Rodin, Anastasia
Marelly, Nitzan
Abraham, Michal
Mishalian, Inbal
Wildbaum, Hila
Katz, Tamar
Baar, Yuval
Yarkoni, Shai
Bakimer-Kleiner, Ronit
Peled, Amnon
Zuckerman, Tsila
Stein, Jerry
author_facet Levy-Barazany, Hilit
Shachnai-Pinkas, Liat
Rodionov, Galina
Saar, Alex
Rosenzwaig, Michal
Gez, Liron
Rodin, Anastasia
Marelly, Nitzan
Abraham, Michal
Mishalian, Inbal
Wildbaum, Hila
Katz, Tamar
Baar, Yuval
Yarkoni, Shai
Bakimer-Kleiner, Ronit
Peled, Amnon
Zuckerman, Tsila
Stein, Jerry
author_sort Levy-Barazany, Hilit
collection PubMed
description Graft versus host disease (GvHD) remains a limiting factor for successful hematopoietic stem cell transplantation (HSCT). T cells and antigen-presenting cells (APCs) are major components of the hematopoietic G-CSF mobilized peripheral blood cell (MPBC) graft. Here we show that a short incubation (2 h) of MPBCs with hexameric Fas ligand (FasL) selectively induces apoptosis of specific donor T cell subsets and APCs but not of CD34(+) cells. FasL treatment preferentially induces apoptosis in mature T cell subsets which express high levels of Fas (CD95), such as T stem cell memory, T central memory, and T effector memory cells, as well as T(H)1 and T(H)17 cells. Anti-CD3/CD28 stimulated T cells derived from FasL-treated-MPBCs express lower levels of CD25 and secrete lower levels of IFN-γ as compared to control cells not treated with FasL. FasL treatment also induces apoptosis of transitional, naïve, memory and plasmablastoid B cells leading to a reduction in their numbers in the graft and following engraftment in transplanted mice. Most importantly, ex vivo treatment of MPBCs with FasL prior to transplant in conditioned NOD-scid IL2Rγ(null) (NSG) mice prevented GvHD while preserving graft versus leukemia (GvL) effects, and leading to robust stem cell engraftment.
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spelling pubmed-73296332020-07-07 Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance Levy-Barazany, Hilit Shachnai-Pinkas, Liat Rodionov, Galina Saar, Alex Rosenzwaig, Michal Gez, Liron Rodin, Anastasia Marelly, Nitzan Abraham, Michal Mishalian, Inbal Wildbaum, Hila Katz, Tamar Baar, Yuval Yarkoni, Shai Bakimer-Kleiner, Ronit Peled, Amnon Zuckerman, Tsila Stein, Jerry Bone Marrow Transplant Article Graft versus host disease (GvHD) remains a limiting factor for successful hematopoietic stem cell transplantation (HSCT). T cells and antigen-presenting cells (APCs) are major components of the hematopoietic G-CSF mobilized peripheral blood cell (MPBC) graft. Here we show that a short incubation (2 h) of MPBCs with hexameric Fas ligand (FasL) selectively induces apoptosis of specific donor T cell subsets and APCs but not of CD34(+) cells. FasL treatment preferentially induces apoptosis in mature T cell subsets which express high levels of Fas (CD95), such as T stem cell memory, T central memory, and T effector memory cells, as well as T(H)1 and T(H)17 cells. Anti-CD3/CD28 stimulated T cells derived from FasL-treated-MPBCs express lower levels of CD25 and secrete lower levels of IFN-γ as compared to control cells not treated with FasL. FasL treatment also induces apoptosis of transitional, naïve, memory and plasmablastoid B cells leading to a reduction in their numbers in the graft and following engraftment in transplanted mice. Most importantly, ex vivo treatment of MPBCs with FasL prior to transplant in conditioned NOD-scid IL2Rγ(null) (NSG) mice prevented GvHD while preserving graft versus leukemia (GvL) effects, and leading to robust stem cell engraftment. Nature Publishing Group UK 2020-05-20 2020 /pmc/articles/PMC7329633/ /pubmed/32433499 http://dx.doi.org/10.1038/s41409-020-0941-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Levy-Barazany, Hilit
Shachnai-Pinkas, Liat
Rodionov, Galina
Saar, Alex
Rosenzwaig, Michal
Gez, Liron
Rodin, Anastasia
Marelly, Nitzan
Abraham, Michal
Mishalian, Inbal
Wildbaum, Hila
Katz, Tamar
Baar, Yuval
Yarkoni, Shai
Bakimer-Kleiner, Ronit
Peled, Amnon
Zuckerman, Tsila
Stein, Jerry
Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title_full Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title_fullStr Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title_full_unstemmed Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title_short Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance
title_sort brief ex vivo fas-ligand incubation attenuates gvhd without compromising stem cell graft performance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329633/
https://www.ncbi.nlm.nih.gov/pubmed/32433499
http://dx.doi.org/10.1038/s41409-020-0941-2
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