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Effector Stage (effector + stage)
Selected AbstractsEfficient help for autoreactive B-cell activation requires CD4+ T-cell recognition of an agonist peptide at the effector stageEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2009Brian D. Hondowicz Abstract T-cell recognition of peptide/MHC complexes is flexible and can lead to differential activation, but how interactions with agonist (full activation) or partial agonist (suboptimal activation) peptides can shape immune responses in vivo is not well characterized. We investigated the effect of stimulation by agonist or partial agonist ligands during initial CD4+ T-cell priming, and subsequent T-B-cell cognate interactions, on antibody production by anti-chromatin B cells. We found that autoantibody production required TCR recognition of an agonist peptide at the effector stage of B-cell activation. However, interaction with a weak agonist ligand at this effector stage failed to promote efficient autoantibody production, even if the CD4+ T cells were fully primed by an agonist peptide. These studies suggest that the reactivity of the TCR for a target self-peptide during CD4+ T-B-cell interaction can be a critical determinant in restraining anti-chromatin autoantibody production. [source] Matrix Regulation of Skeletal Cell Apoptosis II: Role of Arg-Gly-Asp-Containing PeptidesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002Robert L. Perlot Jr. Abstract This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells. [source] 4255: Integrating the interplay between innate and adaptive immunity in the development of non infectious uveitisACTA OPHTHALMOLOGICA, Issue 2010AD DICK Purpose Whilst uveitis is a CD4 T cell mediated disease, there remains both the interplay with innate immunity at both the affector (initiation) of disease and moreso the phenotype and severity of the effector stages of disease. Methods The talk will describe the experimental evidence to describe the interplay of T cells and myeloid cells within the retina during intraocular inflammation. Results TNF, whilst a pleitropic cytokine, has significant influence of the disease phenotype and disease course we observe experimentally. TNF is requred for activation of myeloid cells (macrophages)when in presence of Th1 CD4 T cells, which results in contribution to tissue damage but also controlling T cell proliferation in situ via generation of myeloid suppressor cells. Moreover, the role of resident myeloid cells (microglia) is to down-regulate the immune response. The role of myeloid cells in the healing response and angiogenesis will also be discussed with respect to T cell responses. Conclusion Myeloid cells are actively conditioned by their envirnoment (cognate and soluble factors) to respond accordingly. As such the regulation of immune response and healing that follows is dictated by the innate system in response to changes in local and systemic conditions. [source] | ||||||||||