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Oligomannose-coated liposomes (OMLs), containing entrapped antigens, serve as effective antigen delivery vehicles and as a novel adjuvant to induce antigen-specific cellular immune responses. However, in vitro activation of antigen-presenting cells (APCs) by OMLs has not yet been demonstrated. In this paper, we found that OMLs can deliver the antigens and the stimulatory signals into inflammatory monocytes in vitro , leading to differentiation of the cells to mature APCs. When OMLs were co-cultured with peripheral blood mononuclear cells from C57BL/6 mice in the presence of mouse serum, OMLs were preferentially incorporated into both Ly6C high monocytes and Ly6C low monocytes, which are referred to as murine inflammatory and resident monocytes, respectively. The expression of CD11c, CD80, CD86, CCR7, and MHC class II on the Ly6C high monocytes was significantly enhanced during the 24 h after OML uptake, whereas upregulation of these molecules on the Ly6C low monocytes was limited. In addition, the antigenic peptide of OVA encased in OMLs was presented on MHC class I of only Ly6C high monocytes. Furthermore, OVA-encasing OML-ingesting monocytes can activate CD8 + T cells from OT-1 mice, suggesting that antigens encapsulated in OMLs were cross-presented in inflammatory monocytes. Adoptive transfer of the monocytes that engulf OVA-encasing OMLs led to induction of an antigen-specific Th1 immune response in mice. Taken together, mature APCs can be generated from inflammatory monocytes in peripheral blood by ex vivo treatment of the cells with OMLs without any additional stimuli. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes an immune-inspired system based on an alternate theory about the self–nonself distinction theory, which defines the negative selection process as a mechanism of a fuzzy system based on the affinity between antigen and T-cells. This theory may provide a decision making tool which improves the generation of detectors or even define new data monitoring in order to detect an extreme variation of the system behavior, which means anomalies occurrences. Through these algorithms, tests are performed to detect faults of a DC motor. Upon detection of faults, a participatory clustering algorithm is used to classify these faults and tested to obtain the best set of parameters to achieve the most accurate clustering for these tests in the application being discussed in the article. [Copyright &y& Elsevier]

Abstract: We develop and analyze a model for the interactions of T-cells, antigen presenting cells (APCs), and HIV-1. Our model consists of five components: APCs, resting helper T-cells, activated uninfected helper T-cells, activated and infected helper T-cells, and the free virus. We emphasize the impact of APCs during HIV infection and the cell-to-cell contact manner in the transference of HIV-1 in vivo. The existence and stability of the uninfected steady state and those of the infected steady states are discussed. The uniform persistence of the system is also obtained. As a novel approach, multiple exposures of HIV-1 are illustrated and discussed in the paper. Through numerical stimulations, we check the sensitivity of APCs and helper T-cells in impacting the infection outcome and obtain some relevant results. We also give the lowest infectioe dose for certain individuals. [Copyright &y& Elsevier]

Different single-cell analyses for the detection of antigen-specific T cells based on antigen-triggered induction of cytokine production (elispot, intracellular cytokine staining, cytokine secretion assay, etc.) have been analyzed. In this paper we present the data of a thorough validation of the IFNγ Secretion Assay (ISA, Miltenyi Biotec, Bergisch Gladbach, Germany). In this assay the secreted IFNγ is bound to the cell surface and is then stained as an artificial surface molecule and analyzed by flow-cytometry. The introduction of five quality criteria markedly improved the reproducibility of this assay and made it very reliable (intra-assay variability<5%; inter-assay variability<20%). Recovery experiments further demonstrated that almost 100% of IFNγ+ labeled cells could be detected by this technology. In order to analyze which cell subsets contribute to IFNγ-production, we compared the results obtained in different individuals after VZAg-stimulation. Three different IFNγ-secretion patterns could be discerned. In Pattern 1 there is a predominant and almost equal contribution of T cells and NK cells with a minor contribution of CD3+CD56+ and B cells. Pattern 2, which is most abundant, is characterized by a predominance of NK cells (60–70%). Pattern 3 differs from the previous one in its minor contribution of NK cells. Here T cells predominate the IFNγ secretion. These results clearly demonstrate that the IFNγ+ subset distribution after VZAg-stimulation is not uniform and differs individually. Furthermore, the ISA-technology proves to be very useful in vaccine research. This was demonstrated by testing the IFNγ+ secretion pattern after HBsAg-stimulation in PBMC from HBsAg-vaccinated individuals. [Copyright &y& Elsevier]

Given the key role 4-1BB plays in the stimulation of T cells, humanization of agonistic anti-human 4-1BB monoclonal antibody (mAb) may have important clinical applications. In this paper, we present the humanization of agonistic anti-human 4-1BB mAb, BBK-4, using a phage display library. We first prepared the combinatorial library by incorporating murine and human alternative at positions representing buried residues that might affect the structural integrity of the antigen binding site. Six humanized single chain Fv (scFv) fragments were selected from the combinatorial library expressing phage-displayed humanized scFv. They were found to retain the epitope specificity of the original mAb but had affinities of lower than 1/10 of the original. In spite of the lower affinity, the humanized scFv coated on the surface expanded human peripheral blood mononuclear cells (PBMCs) in MLR similarly to the original mAb in the presence of anti-CD3 mAb. These results suggest that humanized anti-human 4-1BB scFvs can be used as a valuable reagent for clinical application. [Copyright &y& Elsevier]

This paper discusses some consequences of the discovery that antigen receptors are degenerate: Immune specificity, in contrast to the tenets of the clonal selection paradigm, must be generated by the immune response down-stream of initial antigen recognition; and specificity is a property of a collective of cells and not of single clones. [Copyright &y& Elsevier]

The entry of exogenous antigen into the MHC class I-restricted crosspresentation pathway can contribute to CD8+ T cell tolerance and immunity, in particular to peripheral self-antigens or selected viruses and bacteria showing restricted tissue tropism. Dendritic cells are the key crosspresenting cells and, as such, they are thought to carry specialized machinery dedicated to this purpose. Two recent papers describe intracellular components tailored to the dendritic cell crosspresentation pathway. [Copyright &y& Elsevier]

Epidermal Langerhans cells are dendritic bone marrow-derived cells which synthesize and express Ia antigens. During the past decade, in vitro studies have demonstrated that they play a critical role in the induction of many types of T-cell responses. Specifically, Langerhans cells are effective antigen-presenting cells in allogeneic and antigen specific proliferative and cytotoxic T-cell responses. This paper reviews these functions and suggests areas of future investigations into the mechanisms involved in T-cell activation by Langerhans cells. [ABSTRACT FROM AUTHOR]

Human genetic and environmental factors underlie susceptibility to the T cell-mediated autoimmune disease, multiple sclerosis (MS). How the environment influences the pathogenesis of MS has been difficult to parse. A recent paper in Cell shows that environmental antigens that activate myelin-specific T cells can be identified with unprecedented accuracy. [Copyright &y& Elsevier]