Examining Factors Critical to T Cell Suppression and Migration During Acute Graft-Versus-Host Disease Public Deposited

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  • March 20, 2019
Creator
  • Dant, Trisha
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • Allogeneic stem cell transplant (allo-SCT) is a curative therapy for malignant and non-malignant diseases. Unfortunately, acute Graft-versus-Host Disease (aGvHD) is a complication of allo-SCT, and is characterized by migration of donor T cells present in the stem cell graft first to secondary lymphoid tissue (SLT) and then to recipient target organs where they cause inflammation and tissue damage. The purpose of the work described herein is to obtain novel insights into aGvHD pathogenesis. Specifically, we examine ways to modulate T cell function in order to reduce aGvHD. We address new ways to suppress donor T cells first by eliminating the Aryl-hydrocarbon Receptor transcription factor, which caused donor T cells to differentiate into Tregs versus Th17 cells in the colon that consequently reduced aGvHD severity. Secondly, we address suppressing donor T cells through providing ex vivo generated ILC2 cells that are eliminated from recipients during the conditioning regimen, which enhanced the accumulation of MDSCs in the GI tract that both prevented and treated aGvHD. Finally, we examined the impact that modulating actin cytoskeletal dynamics has on T cell function during aGvHD by eliminating the actin-binding protein Coronin 1B. Lack of Coronin 1B resulted in attenuated aGvHD and reduced accumulation in SLT and target organs caused by both a reduction in highly proliferative T cells along with increased cell death. Taken together, our research described extends our knowledge of factors important to T cell function during aGvHD.
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Rights statement
  • In Copyright
Advisor
  • Wan, Yisong
  • Serody, Jonathan
  • Whitmire, Jason
  • Hansen, Jonathan
  • Liu, Zhi
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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