Human monocyte-derived dendritic cells express cFLIPL and resist CD95-mediated apoptosis: inhibition by bisindolylmaleimeide

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Production of antineutrophil cytoplasm antibodies derived from circulating B cells in patients with systemic vasculitis

The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. In certain systemic vasculitides, autoimmunity plays an important role with autoantibodies developing towards neutrophils, which are termed antineutrophil cytoplasm antibodies (ANCA). There is a growing body of evidence that T cells may contribute to the pathogenesis of ANCA-associated vasculitides. A system was set up to determine whether B cells require T cell help to produce antibodies in a peripheral blood lymphocyte (PBL) culture system enriched for B cells and dendritic cells (DC). As a control, tetanus toxoid (TT) antibody production was detected from individuals not recently immunized with tetanus vaccine when stimulated with TT antigen. Proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies were produced from B cell and DC enriched cultures prior to the addition of antigen in some ANCA-positive patients with high ANCA titres, but not from patients with low ANCA titres or controls. PBMC from individuals recently immunized with tetanus vaccine were also maximally stimulated in that addition of antibody did not enhance antibody production. We conclude that this system supports a role for T cell help in the production of TT antibodies in individuals not immunized recently with tetanus vaccine. However, in patients with ANCA-associated vasculitis and controls recently immunized with tetanus vaccine, circulating B cells are apparently spontaneously producing autoantibody, possibly reflecting a system already maximally driven in vivo, and therefore masking underlying potential T cell-B cell collaboration. Such B cells may be less responsive to regulatory stimuli in vivo

The 'kiss of death' by dendritic cells to cancer cells

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) specialized in the stimulation of naïve T lymphocytes, which are key components of antiviral and antitumor immunity. DCs are 'sentinels' of the immune system endowed with the mission to (1) sense invading pathogens as well as any form of tissue distress and (2) alert the effectors of the immune response. They represent a very heterogeneous population including subsets characterized by their anatomical locations and specific missions. Beyond their unique APC features, DCs exhibit a large array of effector functions that play critical roles in the induction and regulation of the cell-mediated as well as humoral immune responses. In the course of the antitumor immune response, DCs are unique in engulfing tumor cells killed by natural killer (NK) cells and cross-presenting tumor-associated antigens to cytotoxic T lymphocytes (CTLs). However, while DCs mediate antitumor immune responses by stimulating tumor-specific CTLs and NK cells, direct tumoricidal mechanisms have been recently evoked. This review addresses the other face of DCs to directly deliver apoptotic signals to stressed cells, their role in tumor cell death, and its implication in the design of DC-based cancer immunotherapies.link_to_subscribed_fulltex