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The oral route is considered to be the main entry site of several transmissible spongiform encephalopathies or prion diseases of animals and man. Following natural and experimental oral exposure to scrapie, sheep first accumulate disease associated prion protein (PrP (d) ) in Peyer's patch (PP) lymphoid follicles. In this study, recombinant ovine prion protein (rPrP) was inoculated into gut loops of young lambs and the transportation across the intestinal wall studied. In particular, the immunohistochemical phenotypes of cells bearing the inoculated prion protein were investigated. The rPrP was shown to be transported across the villi of the gut, into the lacteals and submucosal lymphatics, mimicking the transport route of PrP (d) from scrapie brain inoculum observed in a previous intestinal loop experiment. The cells bearing the inoculated rPrP were mainly mononuclear cells, and multicolor immunofluorescence procedures were used to show that the rPrP bearing cells were professional antigen presenting cells expressing Major histocompatibility complex II (MHCII). In addition, the rPrP bearing cells labeled with CD205, CD11b and the macrophage marker CD68, and not with the dendritic cell markers CD11c and CD209. Others have reported that cells expressing CD205 and CD11b in the absence of CD11c have been shown to induce T cell tolerance or regulatory T cells. Based on this association, it was speculated that the rPrP and by extension PrP (d) and scrapie infective material may exploit the physiological process of macromolecular uptake across the gut, and that this route of entry may have implications for immune surveillance.

In patients with ulcerative colitis (UC) the cumulative risk of colon cancer is lower than the actual rate of dysplasia suggesting an efficient immune surveillance mechanism. Since the co-stimulatory molecule CD80 is overexpressed in dysplastic colonic mucosa of UC patients and T-cell activation entails effective costimulation, we aimed to evaluate the functional implication of CD80 signaling in colonic UC-associated carcinogenesis. In humans, we observed that the percentage of CD80+ and HLA-A+ IEC was increased in the dysplastic colonic mucosa of UC patients. In vitro, IEC activated CD8+ T-cells through a CD80-dependent pathway. Finally, in the AOM/DSS-induced colonic adenocarcinoma model CD80 signaling inhibition significantly increased the frequency and extension of high-grade dysplasia, whereas enhancing CD80 activity with an anti-CTLA4 antibody significantly decreased colonic dysplasia. In conclusion, CD80 signaling between IEC and T-cells represents a key factor controlling the progression from low to high grade dysplasia in inflammatory colonic carcinogenesis.

Success of pregnancy depends on many factors. Three phenomena inducing immune tolerance against semi-allogeneic conceptus may play a crucial role in the pre-implantation period of pregnancy: influence of sex hormones in sex cycle, presence of oocyte or embryo and the presence of semen in the female reproductive tract. On the other hand dendritic cells are the most effective antigen-presenting cells in regulation of immune phenomena and also are considered as potent participants in inducing immune tolerance in the pregnancy. They communicate with T cells in cell contact-dependent manner or via cytokines. During cell-cell contacts, costimulatory molecules play a key role and their expression is often dependent on cytokines milieu. Both costimulatory molecules and cytokines influence generation of T regulatory cells. Interactions of these molecules are closely related. In this paper we would like to pay attention to the importance of antigen presenting cells costimulatory potency in immune regulation during a pre-implantation period of pregnancy.

[EN] Review paper [ES] Artículo de Revisión, Immunological synapses (IS) are emerging as highly organized 3D structures -formed by surface and cytoplasmic signalling and cytoskeletal molecules - that assemble at the zone of contact between a T cell and an antigen presenting cell (APC). The IS control functions that allow APC and T cells modulate the immune response., This work was supported by the Ministerio de Educación y Ciencia (grants BFI-2001-0228 and SAF2005-00801) and Red de Investigación en Inflamación y en Enfermedades Reumáticas (RIER) (grant RD08/0075 (RETICS Program/Instituto de Salud Carlos III)) (J.L.R.-F.), a scholarship associated with grant PI021058, conferred by the Fondo de Investigación Sanitaria (L.R.-B.), and fellowship Formación de Personal Investigador (FPI) conferred by the Ministerio de Educación y Ciencia (C.D.-M.).

Langerhans cells (LCs) were first described by Paul Langerhans, in 1868, as dendritically shaped cells, which were located in the squamous epithelia of epidermis. Later on, these cells were identified in all stratified squamous epithelium of mammals. Dendritic cells (DCs) play an important role in local defense mechanisms in the epithelium. LCs are situated usually in the suprabasal layer of stratified squamous epithelia of oral mucosa and epidermis of skin. They constitute 3% of the cell population in epidermis. LCs are thought to act as antigen presenting cells (APCs) during initiation of immune responses. With the help of APCs, the lymphocytes are able to recognize and respond to specific microbes. In this paper we have reviewed the origin, distribution, demonstration and mechanism of action of LCs and their role in different pathological conditions.

Summary The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n=67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver.