In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4 T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.
View Article and Find Full Text PDFTherapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs.
View Article and Find Full Text PDFThe importance of monocyte-derived dendritic cells (DCs) is evidenced by the fact that they are essential for the elimination of pathogens. Although in vitro DCs can be generated by treatment of monocytes with GM-CSF and IL-4, it is unknown what stimuli induce differentiation of DCs in vivo. CD137L-DCs are human monocyte-derived DC that are generated by CD137 ligand (CD137L) signaling.
View Article and Find Full Text PDFCD137 is expressed on activated T cells and NK cells, among others, and is a potent co-stimulator of antitumor immune responses. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), and CD137L reverse signaling into APC enhances their activity. CD137-CD137L interactions as main driver of type 1, cell-mediated immune responses explains the puzzling observation that CD137 agonists which enhance antitumor immune responses also ameliorate autoimmune diseases.
View Article and Find Full Text PDFCD137 ligand (CD137L) is expressed on APCs and crosslinks CD137, a powerful costimulatory molecule on T cells during cognate interactions, and thereby greatly enhances immune responses. We report that CD137 can be transferred from activated T cells and from tumor cells that express CD137 to other cells via trogocytosis. This trogocytic transfer is independent of CD137L expression by the recipient cell.
View Article and Find Full Text PDFCD137 ligand (CD137L) has emerged as a powerful regulator of myelopoiesis that links emergency situations, such as infections, to the generation of additional myeloid cells, and to their activation and maturation. CD137L is expressed on the cell surface of hematopoietic stem and progenitor cells (HSPC) and antigen presenting cells (APC) as a transmembrane protein. The signaling of CD137L into HSPC induces their proliferation and differentiation to monocytes and macrophages, and in monocytes CD137L signaling induces differentiation to potent dendritic cells (DC).
View Article and Find Full Text PDFDendritic cells (DCs) are highly potent initiators of adaptive immune responses and, as such, represent promising tools for immunotherapeutic applications. Despite their potential, the current efficacy of DC-based immunotherapies is poor. CD137 ligand (CD137L) signaling has been used to derive a novel type of DCs from human peripheral blood monocytes, termed CD137L-DCs.
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