Article (Scientific journals)
Xenogeneic graft-versus-host disease in humanized NSG and NSG-HLA-A2/HHD mice
Ehx, Grégory; SOMJA, Joan; Warnatz, Hans-Jörg et al.
2018In Frontiers in Immunology, 9, p. 1943
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Keywords :
GVHD; xenogeneic; NSG; NSG-HLA-A2/HHD; TCR receptor; TCRb repertoire; RNA sequencing; graft-versus-leukemia
Abstract :
[en] Despite the increasing use of humanized mouse models to study new approaches of graft-versus-host disease (GVHD) prevention, the pathogenesis of xenogeneic GVHD (xGVHD) in these models remains misunderstood. The aim of this study is to describe this pathogenesis in NOD/LtSz-PrkdcscidIL2rgtm1Wjl (NSG) mice infused with human PBMCs and to assess the impact of the expression of HLA-A0201 by NSG mice cells (NSG-HLA-A2/HHD mice) on xGVHD and graft-versus-leukemia (GvL) effects, by taking advantage of next-generation technologies. We found that T cells recovered from NSG mice after transplantation had upregulated expression of genes involved in cell proliferation, as well as in TCR, co-stimulatory, IL-2/STAT5, mTOR and Aurora kinase A pathways. T cells had mainly an effector memory or an effector phenotype and exhibited a Th1/Tc1-skewed differentiation. TCRb repertoire diversity wasmarkedly lower both in the spleen and lungs (a xGVHD target organ) than at infusion. There was no correlation between the frequencies of specific clonotypes at baseline and in transplanted mice. Finally, expression of HLA-A0201 by NSG mice led to more severe xGVHD and enhanced GvL effects toward HLA-A2+ leukemic cells. Altogether our data demonstrate that the pathogenesis of xGVHD shares important features with human GVHD and that NSG-HLA-A2/HHD mice could serve as better model to study GVHD and GvL effects.
Disciplines :
Hematology
Author, co-author :
Ehx, Grégory  ;  Université de Liège > GIGA-R : Hématologie
SOMJA, Joan ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
Warnatz, Hans-Jörg
Ritacco, Caroline ;  Université de Liège - ULiège > GIGA-R : Hématologie
HANNON, Muriel ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - endocrino - métabolique
Delens, Loïc ;  Université de Liège - ULiège > GIGA-R : Hématologie
Fransolet, Gilles 
DELVENNE, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
Muller, Joséphine ;  Université de Liège - ULiège > GIGA-R : Hématologie
BEGUIN, Yves  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique
Lehrach, Hans
Belle, Ludovic ;  Université de Liège - ULiège > GIGA-R : Hématologie
Humblet-Baron, Stéphanie
BARON, Frédéric  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique
More authors (4 more) Less
Language :
English
Title :
Xenogeneic graft-versus-host disease in humanized NSG and NSG-HLA-A2/HHD mice
Publication date :
2018
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Media S.A., Switzerland
Volume :
9
Pages :
1943
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 08 September 2018

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