Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell–produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection.

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a “full” peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.

It is now appreciated that the range of ligands interacting with C-type lectin type receptors on antigen presenting cells includes endogenous self-molecules as well as pathogens and pathogen-derived ligands. Interestingly, not all interactions between these receptors and pathogenic ligands have beneficial outcomes, and it appears that some pathogens have evolved immunoevasive or immunosuppressive activities through receptors such as DC-SIGN. In addition to this, recent data indicate that the well-characterised macrophage mannose receptor is not essential to host defence against fungal pathogens, as previously thought, but has an important role in regulating endogenous glycoprotein clearance. New studies have also demonstrated that different ligand binding and/or sensing receptors collaborate for full and effective immune responses.

The nude mutation (nu) The thymus is the obligatory site of T-cell maturation and is therefore central to the development of a fully competent immune system; athymia results in profound immunodeficiency (1). The thymic epithelium not only supplies a framework in which T-cell development occurs, it also shapes the T-cell repertoire by mediating positive and negative selection of developing thymocytes. Consequently, its organization is quite complex (2).The nude mutation (nu) has a profound effect on thymic development (3, 4) but does not affect the lymphoid compartment (4, 5). During development of the nude thymic anlage, the pharyngeal ectoderm of the third cleft fails to proliferate at embryonic day 11.5 (6) and thymogenesis does not progress beyond this point; the anlage is devoid of lymphocytes and never proceeds to a lymphoid stage (4). Adult nude mice retain a nonfunctional cystic thymic rudiment (7).Two hypotheses have previously been offered to explain the nu defect (6,8

An antigen administered orally can induce immunological tolerance to a subsequent challenge with the same antigen. Evidence has been provided for the efficacy of this approach in the treatment of human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. However, oral administration of autoantigen in mice was found to induce a cytotoxic T lymphocyte response that could lead to the onset of autoimmune diabetes. Thus, feeding autoantigen can cause autoimmunity, which suggests that caution should be used when applying this approach to the treatment of human autoimmune diseases.

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A class I histocompatibility gene, H-2Kb, linked to the rat insulin promoter, is overexpressed in the pancreatic beta cells of transgenic mice. The mice, whether syngeneic or allogeneic to the transgene, develop insulin dependent diabetes without detectable T cell infiltration, suggesting a direct, non-immune role for the transgenic class I molecules in the disease process.

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