Xenogeneic Graft-Versus-Host Disease in Humanized NSG and NSG-HLA-A2/HHD Mice

Frontiers in Immunology
Grégory EhxFrédéric Baron

Abstract

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-PrkdcscidIL2rγtm1Wjl (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. TCRβ repertoire diversity was markedly 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...Continue Reading

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Citations

Aug 8, 2020·Journal of Cellular and Molecular Medicine·Shanshan ZhaoGuihua Hou
Jan 30, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Grégory EhxFrédéric Baron
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Nov 13, 2021·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Qiaozhi JiangRenchuan Tao

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Datasets Mentioned

BETA
E-MTAB-6865

Methods Mentioned

BETA
flow cytometry
flow
PCR
RNA-seq
Assay
flow-cytometry
RNAseq

Software Mentioned

Plex Manager Software
Illumina BaseSpace
Flowjo
Graphpad
STAR
GSEA
Bio
RNA Alignment
IgorPro
Plex System

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