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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study.Methods: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde-modified allergoid (HDM-GA) to induce the proliferation and cytokine production by fresh PBMC and by DC-stimulated polyclonal Th cells and HDM-specific Th cell clones.Results: Freshly isolated T cells showed a partially reduced responsiveness to HDM-GA, differentially pronounced in different donors. HDM-specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM-GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor-dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM-specific T cell clones.Conclusions: The reduced stimulatory potential of HDM-GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid-nonreactive HDM-specific Th cells may result in differential responses of individual patients to immunotherapy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 29 (1999), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Optimal clearance of the various pathogen types encountered by the human body requires the selective activation of particular cellular and/or humoral immune responses. The orchestration of the types of effector responses is directed by Th cells through the production of type 1 (Th1 cell-associated) and type 2 (Th2 cell-associated) cytokines. The way in which the Th cell cytokine profile is matched to the type of invading pathogen, and why these profiles sometimes derail and lead to disease, is not well understood. Here, we will discuss the concept that antigen-presenting cells (APC) provide Th cells not only with antigen and costimulatory signals, but also with a polarizing signal (signal 3). This signal can be mediated by many APC-derived factors, but IL-12 and PGE2 seem to be of major importance. The Th2-biased responses in atopic allergy appeared to be associated with monocytes with a decreased IL-12/PGE2 ratio and, consequently, with the down-regulation of type 1 cytokine production in Th cells. As for Th cells, APC can be functionialy polarized. In vitro experiments with monocyte-derived dendritic cells (DC) showed that the presence of IFN-γ during activation of immature DC primes for mature DC with the ability of high IL-12 production and, consequently, a Th1-driving capacity (APC1 or DC1). In contrast, PGE2 primes for a low IL-12 production ability and a Th2-driving capacity (APC2 or DC2). These findings suggest that pathogens provoke either Th1- or Th2-cell development by inducing the production of a certain pattern of inflammatory DC-polarizing mediators (e.g. IFN-γ and PGE2) at the site of infection. The type of immune polarization will not only depend on the type of pathogen, but also varies with the type of infected tissue, i.e. that different tissues produce different mediators in response to the same pathogen. In the case of atopic allergy, this concept implies that the Th2-cell bias may be related to low levels of cross-regulatory infections, to Th1 cell-inducing pathogens, or to an aberrant function of stromal cells in peripheral tissues.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Decreased exposure to microbial stimuli has been proposed to be involved in the increased prevalence of atopic disease. Such a relationship was indicated by enhanced presence of typical probiotic bacteria in the intestinal flora correlating with reduced prevalence of atopic disease. Recent clinical trials suggested that probiotic bacteria may decrease and prevent allergic symptoms, but which (different) species or strains may contribute is poorly understood.Objective We sought to select probiotic bacteria by their ability to modulate in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs), to make a rational choice from available strains.Methods PBMCs, purified monocytes, and lymphocytes from healthy donors were co-cultured with 13 different strains of probiotic bacteria. The effect of lactic acid bacteria (LAB) on different cell populations and effects on cytokine production induced by the polyclonal T cell stimulator phytohaemagglutinin (PHA) was evaluated by measuring T helper type 1, T helper type 2 (Th2), and regulatory cell cytokines in culture supernatants by multiplex assay.Results PBMCs cultured with different strains produced large amounts of IL-10 and low levels of IL-12p70, IL-5, and IL-13. In PHA-stimulated PBMC cultures, the tested strains decreased the production of Th2 cytokines. Neutralizing IL-10 production resulted in partial to full restoration of Th2 cytokine production and concurred with an increase in pro-inflammatory cytokines such as IL-12p70 and TNF-α. Within the PBMCs, the CD14+ cell fraction was the main source of IL-10 production upon interaction with LAB.Conclusion Our results indicate that certain strains of lactobacilli and bifidobacteria modulate the production of cytokines by monocytes and lymphocytes, and may divert the immune system in a regulatory or tolerant mode. These specific strains may be favorable to use in prevention or treatment of atopic disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-069X
    Keywords: Memory T cells ; Naive T cells ; Immunodermatopathology ; Skin immune system ; T-cell subsets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Absolute numbers of CD3+ T lymphocytes and their subpopulations were determined and statistically evaluated in the lesional skin of psoriasis, atopic dermatitis, nummular dermatitis, pityriasis rosea, and lichen planus. Skin sections were divided into horizontal layers and the numbers of CD3+ T cells as well as CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets were counted. In addition, absolute numbers of the two subpopulations of inducer T cells, i.e., “memory” (4B4+ 2H4-) and “naive” (4B4- 2H4+) were evaluated. Unexpectedly, epidermal infiltration by T cells was highest in psoriasis and lowest in atopic dermatitis. In most cases, this exocytosis was dominated by CD8+ suppressor/cytotoxic T lymphocytes, with a minimal epidermal mean CD4/mean CD8 ratio of 0.04 in pityriasis rosea and a maximum of 0.48 in psoriasis. Inducer T cells within the epidermis were almost exclusively of the 4B4+ 2H4- “memory” T-cell subpopulation, whereas 4B4- 2H4+ “naive” T cells were extremely uncommon in lesional epidermis. Similar results were obtained for dermal T cells in all diseases studied, i.e., 4B4- 2H4+ “naive” T cells were relatively rare. Papillary dermis infiltration by T cells was highest in lichen planus where a mean CD4/mean CD8 ratio of 1.10, the minimum in this comparative study, was obtained. The mean CD4/mean CD8 ratio of the papillary infiltrate was highest in atopic dermatitis (4.12). Our results indicate disease-specific and significantly different infiltration patterns of T-lymphocyte subsets in the chronic inflammatory dermatoses investigated. The predominant presence of the CD4+ 2H4- “memory” subpopulation of CD4+ T cells in all diseases studied as well as in normal human skin (reported previously) seems to indicate that the skin immune system is rather unidirectional in its increase in this subpopulation of the inducer T-cell subset. This predominance of the “memory” subpopulation thus indicates that most T cells of normal and diseased human skin are already primed, i.e., have already met their specific ligand in a MHC II context.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Lymph node ; Antigen stimulation ; Dendritic cells ; Enzyme- and immunocytochemistry ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Non-lymphoid dendritic cells were isolated from normal and paratyphoid vaccine-stimulated lymph nodes draining the rat skin. They were studied using enzymecytochemical, immunocytochemical and electron-microscopical methods. These cells had an irregular outline and an eccentrically situated nucleus. All showed acid phosphatase activity in a central area and expressed Ia antigen on the plasma membrane. Birbeck granules were exclusively present in dendritic cells isolated from lymph nodes in the induction phase of the immune response. This observation concurs with the presence of Birbeck granules in interdigitating cells in situ during the same period of the immune response. It is concluded that the dendritic cells are the in-vitro equivalents of the non-actively phagocytizing population of interdigitating cells.
    Type of Medium: Electronic Resource
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