Perivascular mast cells regulate vein graft neointimal formation and remodeling.

Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method.

MHC Class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity.

Background: Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive.

Methods And Results: Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis.

Induction of passive EAE using myelin-reactive CD4+ T cells.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS) often used as a model for the early inflammatory stages of multiple sclerosis and also as a model of organ-specific autoimmune disease.This protocol describes the induction of passive EAE in mice, either using T cells isolated from mice primed with myelin antigens, or through the use of naïve TCR transgenic T cells activated in vitro in the presence of myelin-derived antigens.

T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease.

T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE).

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis.

Background: Experimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4(+) T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s).

Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcɛRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity.

Background: IgE antibodies, sequestered into tissues and retained locally by the high-affinity IgE receptor, FcɛRI, on powerful effector cells such as mast cells, macrophages and eosinophils, may offer improvements in the therapy of solid tumours. The chimeric antibody, MOv18 IgE, against the human ovarian carcinoma antigen, folate receptor α (FRα), is more effective than its IgG1 counterpart in xenograft models of ovarian cancer. Although MOv18 IgE binds to a single epitope on FRα and cannot cross-link IgE receptors on basophils, there remains a risk that components in the circulation of ovarian cancer patients might cross-link FRα-MOv18-IgE-receptor-FcɛRI complexes on basophils to cause type I hypersensitivity.

Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment.

In several murine models of autoimmune arthritis, Th17 cells are the dominant initiators of inflammation. In human arthritis the majority of IL-17-secreting cells within the joint express a cytokine phenotype intermediate between Th17 and Th1. Here we show that Th17/1 cells from the joints of children with inflammatory arthritis express high levels of both Th17 and Th1 lineage-specific transcription factors, RORC2 and T-bet.

Enteropathic histopathological features may be associated with Shwachman-Diamond syndrome.

Aim: To review the gastrointestinal mucosal histological features of biopsies from children with Shwachman-Diamond syndrome (SDS) examined at a single specialist centre.

Methods: Search of a clinical database was performed to identify SDS cases and their gastrointestinal biopsies were reviewed for morphological parameters such as crypt:villous ratio, crypt hyperplasia and abnormal inflammatory infiltrates. Histological sections were also immunostained with CD4, CD20 and HLA-DR to determine the nature of the inflammatory infiltrate.