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>