60 research outputs found
Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands.
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model. Stromal, but not hematopoietic, cells were the essential source of Notch ligands during in vivo priming of alloreactive T cells. GVHD could be prevented by selective inactivation of Dll1 and Dll4 in subsets of fibroblastic stromal cells that were derived from chemokine Ccl19-expressing host cells, including fibroblastic reticular cells and follicular dendritic cells. However, neither T cell recruitment into secondary lymphoid organs nor initial T cell activation was affected by Dll1/4 loss. Thus, we have uncovered a pathogenic function for fibroblastic stromal cells in alloimmune reactivity that can be dissociated from their homeostatic functions. Our results reveal what we believe to be a previously unrecognized Notch-mediated immunopathogenic role for stromal cell niches in secondary lymphoid organs after allo-BMT and define a framework of early cellular and molecular interactions that regulate T cell alloimmunity
Immune modulating effects of cyclophosphamide and treatment with tumor lysate/CpG synergize to eliminate murine neuroblastoma
The inhibition effect of mad Honey on corrosion of 2007-type aluminium alloy in 3.5% NaCl solution
Modified cassava starches as potential corrosion inhibitors for sustainable development
Cell growth inhibition in PC-3 human prostate cancer cells after treatment with gamma-radiation and 8-Cl-cAMP
23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23), Oct 24-28, 2004, Amsterdam, Netherland
Host Langerhans cells (LCs) can be therapeutically manipulated In vivo with imiquimod (TLR7 agonist) to augment DLI-mediated GVH and GVL reactivity
Cell growth inhibition in PC-3 human prostate cancer cells after treatment with gamma-radiation and 8-Cl-cAMP
23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23), Oct 24-28, 2004, Amsterdam, Netherland
320: In vivo activation of APCs with TLR ligands and tissue damage rather than amount of host APCs are critical factors that determine DLI-mediated GVL reactivity and GVHD in MHC-matched minor histocompatibility antigen (mHAg)-mismatched chimeras
320: In vivo activation of APCs with TLR ligands and tissue damage rather than amount of host APCs are critical factors that determine DLI-mediated GVL reactivity and GVHD in MHC-matched minor histocompatibility antigen (mHAg)-mismatched chimeras
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