Search results for "Costimulation"
showing 5 items of 5 documents
NKG2D stimulation of CD8(+) T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice
2017
NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8+ T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+ T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8+ T-cell formation. NKG2D-deficiency that is restricted to murine CD8+ T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+ T cells via the Da…
Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease
2012
Background Allergic asthma is a T H 2-promoted hyperreactivity with an immediate, IgE, and mast cell–dependent response followed by eosinophil-dominated inflammation and airway obstruction. Objective Because costimulation by CD28 is essential for T H 2 but not T H 1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite–induced airway inflammation. Methods To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site–specific mouse anti-mouse mAb blocking CD28 engagement. Results We show …
Technical advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FCεRI-dependent mast cell degranulation
2011
ABSTRACT Tregs play a central role in modulating FcɛRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but a…
Microenvironment Regulation of IL23R/IL-23 Axis Drives Chronic Lymphocytic Leukemia (CLL) Progression
2015
Abstract Background : CLL displays a considerable degree of clinical heterogeneity, which is in part ascribable to clone-intrinsic biological features and that are also influenced by clone-extrinsic events related to the microenvironment. Among the dynamics-taking place within the CLL microenvironment, those finalized to the induction of an overly inflammatory milieu may significantly impact on the CLL natural history by hijacking the immunological microenvironment at the same time fostering clone fitness. IL-23 acts as a prototypical pro-inflammatory mediator representing a promising therapeutic target. We analyzed the ability of CLL cells to sense IL-23 through the IL-23R complex (consist…