Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4⁺ T Cells in Graft-versus-Host Disease.

ABSTRACT: Graft-versus-host disease (GVHD) is the most serious complication of allogeneic hematopoietic cell transplantation. Notch signals delivered during the first 48 h after transplantation drive proinflammatory cytokine production in conventional T cells (Tconv) and inhibit the expansion of regulatory T cells (Tregs). Short-term Notch inhibition induces long-term GVHD protection. However, it remains unknown whether Notch blockade blunts GVHD through its effects on Tconv, Tregs, or both and what early Notch-regulated molecular events occur in alloantigen-specific T cells. To address these questions, we engineered T cell grafts to achieve selective Notch blockade in Tconv versus Tregs and evaluated their capacity to trigger GVHD in mice. Notch blockade in Tconv was essential for GVHD protection a

SUBMITTER: Chung J 

PROVIDER: S-EPMC6615974 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature