T cells take directions from supporting cast in graft-versus-host disease.
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only treatment option for several severe hematological malignancies. The development of graft-versus-host disease (GVHD) is a common complication of the procedure and results when donor T cells become activated against recipient-specific antigens. The factors that drive the alloreactive T cell response are not completely understood. In this issue of the JCI, Chung and colleagues present evidence that stromal cells within lymphoid tissue express the Notch ligands Delta-like 1/4 (DLL1 and DLL4), which in turn directly activate T cells. Importantly, inhibition of DLL1/DLL4-mediated Notch signaling in murine HSCT models dramatically reduced GVHD and improved graft survival.
Derk
D
Amsen
D048868:Adaptor Proteins, Signal Transducing; D064591:Allografts; D000818:Animals; D002135:Calcium-Binding Proteins; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D051880:Receptors, Notch / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch