10.3389/fimmu.2018.01943.s001
Grégory Ehx
Grégory
Ehx
Joan Somja
Joan
Somja
Hans-Jörg Warnatz
Hans-Jörg
Warnatz
Caroline Ritacco
Caroline
Ritacco
Muriel Hannon
Muriel
Hannon
Loïc Delens
Loïc
Delens
Gilles Fransolet
Gilles
Fransolet
Philippe Delvenne
Philippe
Delvenne
Joséphine Muller
Joséphine
Muller
Yves Beguin
Yves
Beguin
Hans Lehrach
Hans
Lehrach
Ludovic Belle
Ludovic
Belle
Stéphanie Humblet-Baron
Stéphanie
Humblet-Baron
Frédéric Baron
Frédéric
Baron
Image_1_Xenogeneic Graft-Versus-Host Disease in Humanized NSG and NSG-HLA-A2/HHD Mice.PDF
Frontiers
2018
GVHD
xenogeneic
NSG
NSG-HLA-A2/HHD
TCR receptor
TCRβ repertoire
RNA sequencing
graft-versus-leukemia
2018-08-30 04:22:50
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_Xenogeneic_Graft-Versus-Host_Disease_in_Humanized_NSG_and_NSG-HLA-A2_HHD_Mice_PDF/7027673
<p>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-Prkdc<sup>scid</sup>IL2rγ<sup>tm1Wjl</sup> (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<sup>+</sup> 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.</p>