Logical immunosuppressive network and its putative role in the pathogenesis of
Logical immunosuppressive network and its putative role in the pathogenesis of autoimmunity: inhibition through signaling, cellular contact, anergy, apoptosisH Lorenz, N Blank, M Kriegel, M Schiller, E Scherb, S Winkler, JR Kalden Department of Medicine PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 III, Institute for Clinical Immunology, University of Erlangen uremberg, Erlangen, Germany Arthritis Res Ther 2003, 5(Suppl 3):95 (DOI 10.1186/ar896) A complex cellular system like the human immune system only functions in a tightly regulated balance between activation and inhibition. We therefore hypothesise that defects in immunosuppression might contribute to the pathogenesis of autoimmunity in man. In our work we established a broad basis for testing the function of various immunosuppressive mechanisms in health and autoimmune disease. Signals through certain CD45 epitopes are strongly immunosuppressive in vitro. We therefore hypothesised that we will be able to induce anergy in CD45-treated lymphocytes. As control we used a human leukocyte antigen DR (HLA DR) antibody with equal inhibitory capacities on cell proliferation. We found that HLA DR signals, but not CD45 signals, could induce lymphocytic anergy, which was monocyte dependent. Moreover, these anergic lymphocytes were extremely sensitive for protein kinase C-mediated apoptosis, indicating that immunosuppressive mechanisms are inter-related. We are currently studying the exact prerequisites for this new mode of anergy and apoptosis in cells from normal donors and autoimmune patients. This is especially interesting as we have shown in our previous work that regulation of apoptosis might be disturbed, especially in systemic lupus erythematosus. Shedding of activating surface molecules represents another physiological way to prevent hyperactivation. We have recently identified a family with a mutation close to the protease docking site of tumor necrosis factor alpha converting enzyme in the tumor necrosis factor receptor p55 molecule, leading to a periodic fever syndrome with97 Novel B-lymphocyte-deleting agents for the treatment of autoimmune diseases: induction of the mitochondrial pathway of apoptosisG Silverman, CS Goodyear Department of Medicine, University of California San Diego, La Jolla, California, USA Arthritis Res Ther 2003, 5(Suppl 3):97 (DOI 10.1186/ar898) Background To develop PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25645579 new approaches for the targeted deletion of pathogenic autoimmune B lymphocytes, we have studied a bacterialSAvailable online http://arthritis-research.com/supplements/5/Sproduct, protein A of Staphylococcus aureus (SpA). We have previously discovered that SpA has the properties of a B-cell superantigen, enabling interactions with conserved variable region framework subdomains of the antigen receptors of lymphocytes rather than the complementarity determining region involved in the LuminespibMedChemExpress AUY922 binding of conventional antigens [1]. Exposure to SpA can induce immune tolerance affecting a supraclonal set of lymphocytes [2]. Objective To evaluate the outcome of in vivo SpA treatment. Results Within hours, a sequence of events is initiated only in targeted B cells, with rapid downregulation of B-cell antigen receptor and the coreceptors CD19 and CD21, the induction of an activation phenotype, and limited rounds of proliferation. Massive B-cell-specific apoptosis then occurs through a process heralded by the dissipation of mitochondrial membrane potential, followed later by the induction of the caspase pathway and DNA fragmentation. Post exposure, B-cell apop.
