In Vitro Th17-Polarized Human CD4+ T Cells Exacerbate Xenogeneic Graft-versus-Host Disease
- PMID: 30326279
- DOI: 10.1016/j.bbmt.2018.10.007 (VSports注册入口)
In Vitro Th17-Polarized Human CD4+ T Cells Exacerbate Xenogeneic Graft-versus-Host Disease (V体育官网)
Abstract
Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. The role of Th17 cells in its pathophysiology remains a matter of debate VSports手机版. In this study, we assessed whether enrichment of human peripheral blood mononuclear cells (PBMCs) with in vitro Th17-polarized CD4+ T cells would exacerbate xenogeneic GVHD (xGVHD) into NOD-scid IL-2Rγ null (NSG) mice. Naive human CD4+ T cells were stimulated under Th17-skewing conditions for 8 to 10 days and then coinjected in NSG mice with fresh PBMCs from the same donor. We observed that Th17-polarized cells engrafted and migrated toward xGVHD target organs. They also acquired a double-expressing IL-17A+IFNγ+ profile in vivo. Importantly, cotransfer of Th17-polarized cells (1 × 106) with PBMCs (1 × 106) exacerbated xGVHD compared with transplantation of PBMCs alone (2 × 106). Furthermore, PBMC cotransfer with Th17-polarized cells was more potent for xGVHD induction than cotransfer with naive CD4+ T cells stimulated in nonpolarizing conditions (Th0 cells, 1 × 106 + 1 × 106 PBMCs) or with Th1-polarized cells (1 × 106 + 1 × 106 PBMCs). In summary, our results suggest that human Th17-polarized cells can cooperate with PBMCs and be pathogenic in the NSG xGVHD model. .
Keywords: Graft-versus-host disease; Graft-versus-tumor; IL-17A; NSG; Th17; Xenogeneic V体育安卓版. .
Copyright © 2018. Published by Elsevier Inc. V体育ios版.
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