Identifying the science and technology dimensions of emerging public policy issues through horizon scanning.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique.

Salmonella typhimurium infection triggers dendritic cells and macrophages to adopt distinct migration patterns in vivo.

The presence of an anti-bacterial T cell response and evidence of bacterial products in inflamed joints of reactive arthritis patients suggests an antigen transportation role in this disease for macrophages and dendritic cells. We have investigated the functional properties and in vivo migration of macrophages and DC after infection with Salmonella enterica serovar Typhimurium (S. typhimurium).

HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors.

HLA-B27 transgenic rats and strains of HLA-B27-transgenic beta(2)-microglobulin (beta(2)m)-deficient mice develop a multisystem inflammatory disease affecting the joints, skin, and bowel with strong similarity to human spondyloarthritis. We show that HLA-B27 transgenic mice and rats express HC10-reactive, beta(2)m-free HLA-B27 homodimers (B27(2)) and multimers, both intracellularly and at the cell surface of leukocytes, including rat dendritic cells. Fluorescent-labeled tetrameric complexes of HLA-B27 homodimers (B27(2) tetramers) bind to populations of lymphocytes, monocytes, and dendritic cells.

Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR transgenic mice.

The strong association of HLA B27 with spondyloarthropathies contrasts strikingly with most autoimmune diseases, which are HLA class II associated and thought to be mediated by CD4+ T lymphocytes. By introducing a human-derived HLA B27-restricted TCR into HLA B27 transgenic mice, we have obtained a functional TCR transgenic model, GRb, dependent on HLA B27 for response. Surprisingly, HLA B27 supported CD4+ as well as CD8+ T cell responses in vivo and in vitro.

Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions.

The human major histocompatibility complex (MHC) class I allele HLA-B27 is strongly associated with seronegative spondyloarthropathies including ankylosing spondylitis and reactive arthritis. Although of unknown aetiology, one hypothesis suggests that a cytotoxic T cell (CTL) response against a self-antigen at sites of inflammation, such as entheses or joints may be involved. The chondrocyte is one of the major specialized cell types found both in articular cartilage and cartilaginous entheses and therefore is a possible source of such an antigen.