Identification of stem cell transcriptional programs normally expressed in embryonic and neural stem cells in alloreactive CD8+ T cells mediating graft-versus-host disease.

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Koji KatoYi Zhang

Abstract

A hallmark of graft-versus-host-disease (GVHD), a life-threatening complication after allogeneic hematopoietic stem cell transplantation, is the cytopathic injury of host tissues mediated by persistent alloreactive effector T cells (T(E)). However, the mechanisms that regulate the persistence of alloreactive T(E) during GVHD remain largely unknown. Using mouse GVHD models, we demonstrate that alloreactive CD8(+) T(E) rapidly diminished in vivo when adoptively transferred into irradiated secondary congenic recipient mice. In contrast, although alloreactive CD8(+) T(E) underwent massive apoptosis upon chronic exposure to alloantigens, they proliferated in vivo in secondary allogeneic recipients, persisted, and caused severe GVHD. Thus, the continuous proliferation of alloreactive CD8(+) T(E), which is mediated by alloantigenic stimuli rather than homeostatic factors, is critical to maintaining their persistence. Gene expression profile analysis revealed that although alloreactive CD8(+) T(E) increased the expression of genes associated with cell death, they activated a group of stem cell genes normally expressed in embryonic and neural stem cells. Most of these stem cell genes are associated with cell cycle regulation, DNA replic...Continue Reading

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Citations

Jul 23, 2015·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Y EriguchiT Teshima
Apr 7, 2015·Trends in Molecular Medicine·Atsushi Onodera, Toshinori Nakayama
Mar 26, 2014·Molecular and Cellular Biology·Shuaiying CuiJames Douglas Engel
Apr 25, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qing TongYi Zhang
Jan 31, 2018·Nature Reviews. Immunology·Amanda N HenningNicholas P Restifo

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