Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transpla...

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Published inFrontiers in immunology Vol. 15; p. 1411392
Main Authors Shaikh, Ahmad, Gangaplara, Arunakumar, Kone, Abdoul, Almengo, Katherine, Kabore, Mariama D., Ali, Mohamed A.E., Xu, Xin, Saxena, Ankit, Lopez-Ocasio, Maria, McCoy, J. Philip, Fitzhugh, Courtney D.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 16.09.2024
Subjects
Animals
chimerism
Galectin 1 - immunology
Galectin 1 - metabolism
galectin-1
Graft Rejection - immunology
Graft Survival - immunology
haplo-HCT
Hematopoietic Stem Cell Transplantation
Immune Tolerance
Immunology
Major Histocompatibility Complex - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes, Regulatory - immunology
tolerance
Transplantation, Homologous
Tregs
haplo-HCT
chimerism
Tregs
tolerance
galectin-1
Online AccessGet full text
ISSN1664-3224
1664-3224
DOI10.3389/fimmu.2024.1411392

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Abstract Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4 + T cells, CD8 + T cells, natural killer cells, IFN-γ and TNF-α producing CD4 + T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios + , IL-10-producing CD4 + T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1 + Gal-1 + cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
AbstractList Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4 T cells, CD8 T cells, natural killer cells, IFN-γ and TNF-α producing CD4 T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios , IL-10-producing CD4 T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1 Gal-1 cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4 + T cells, CD8 + T cells, natural killer cells, IFN-γ and TNF-α producing CD4 + T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios + , IL-10-producing CD4 + T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1 + Gal-1 + cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Author Gangaplara, Arunakumar
Saxena, Ankit
Almengo, Katherine
Ali, Mohamed A.E.
Xu, Xin
Fitzhugh, Courtney D.
Kabore, Mariama D.
McCoy, J. Philip
Shaikh, Ahmad
Kone, Abdoul
Lopez-Ocasio, Maria
AuthorAffiliation 3 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University , Abha , Saudi Arabia
1 Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , United States
5 Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , United States
2 Department of Biology, The Catholic University of America , Washington, DC , United States
4 Miltenyi Biotec, Research and Development , Gaithersburg, MD , United States
AuthorAffiliation_xml – name: 3 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University , Abha , Saudi Arabia
– name: 5 Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , United States
– name: 4 Miltenyi Biotec, Research and Development , Gaithersburg, MD , United States
– name: 1 Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , United States
– name: 2 Department of Biology, The Catholic University of America , Washington, DC , United States
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  surname: Ali
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  surname: Xu
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Copyright © 2024 Shaikh, Gangaplara, Kone, Almengo, Kabore, Ali, Xu, Saxena, Lopez-Ocasio, McCoy and Fitzhugh 2024 Shaikh, Gangaplara, Kone, Almengo, Kabore, Ali, Xu, Saxena, Lopez-Ocasio, McCoy and Fitzhugh
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Keywords haplo-HCT
chimerism
Tregs
tolerance
galectin-1
Language English
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Edited by: Nicolaus Kröger, University Medical Center Hamburg-Eppendorf, Germany
Elias Toubi, Technion Israel Institute of Technology, Israel
These authors have contributed equally to this work
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Snippet Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major...
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StartPage 1411392
SubjectTerms Animals
chimerism
Galectin 1 - immunology
Galectin 1 - metabolism
galectin-1
Graft Rejection - immunology
Graft Survival - immunology
haplo-HCT
Hematopoietic Stem Cell Transplantation
Immune Tolerance
Immunology
Major Histocompatibility Complex - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes, Regulatory - immunology
tolerance
Transplantation, Homologous
Tregs
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Title Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation
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