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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 33 (1988), S. 1305-1315 
    ISSN: 1573-2568
    Keywords: intestinal immunity ; interleukin 2 ; lymphokine-activated killer cells ; cytotoxicity ; immunoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is evidence indicating that interleukin 2 may be important in the regulation of intestinal immunity, as suggested by its capacity to induce nonspecific cytotoxic (lymphokine-activated killer) activity from human intestinal mucosal mononuclear cells. The present study was designed to further explore the phenotypic and functional changes induced by interleukin 2 on intestinal lymphocytes derived from inflammatory bowel disease and control tissues. Immunohistology of intestinal mucosa demonstrated few cells bearing the activation antigen recognized by anti-Tac (anti-interleukin 2 receptor) monoclonal antibody. However, when isolated lamina proprial mononuclear cells were exposed to interleukin 2 in culture, the number of Tac-positive cells increased dramatically, a phenomenon paralleled by the generation of lymphokine-activated killer cell activity. This cytotoxic function was critically dependent on the continuous availability of interleukin 2, but not on the expression of the Tac antigen, since Tac-negative cells were also cytotoxic. Depletion of natural killer cells, fractionation into T cell-enriched and -depleted cells before and after culturing with interleukin 2, and separation into Tac-positive and -negative cells after interleukin 2 activation failed to eliminate lymphokine-activated killer cell activity, suggesting that this phenomenon is mediated by phenotypically and functionally heterogeneous cell subsets. During the induction of lymphokine-activated killer cells variable amounts of interferon-γwere produced, but these did not correlate with the degree of cytotoxicity. No differences were observed between the response to interleukin 2 by inflammatory bowel disease and control cells. Therefore, in view of its capacity to induce significant phenotypic and functional changes in different subpopulations of intestinal mucosal mononuclear cells, interleukin 2 should be regarded as an important modulator of intestinal immune reactivity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2568
    Keywords: HLA-DR antigens ; interferon γ ; intestinal immunity ; Crohn's disease ; ulcerative colitis ; inflammatory bowel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of HLA-DR antigens on the surface of immune cells is crucial for appropriate antigen presentation and a normal immune response. In the intestinal mucosa involved by Crohn's disease and ulcerative colitis the expression of HLA-DR antigens is increased in both immune and nonimmune cells, a phenomenon probably mediated by soluble factors, such as interferon γ, produced by locally activated mononuclear cells. This study investigated the production of interferon γ by inflammatory bowel disease and control intestinal lamina propria mononuclear cells, and the ability of this endogenously produced lymphokine to induce expression of HLA-DR antigens on the monocytic cell lines U937 and ML3. After in vitro stimulation with interleukin 2 or phytohemagglutinin, but not spontaneously, lamina propria mononuclear cells produced variable amounts of interferon γ, and their culture supernatants could induce de novoexpression of HLA-DR antigens on the monocytic indicator cells. When the mononuclear cells were derived from inflammatory bowel disease mucosa, both the amount of interferon γ present in the supernatants and the number of HLA-DR-positive cells induced by these supernatants were decreased as compared to controls. These results suggest that, in inflammatory bowel disease, interferon γ may not be the only mediator of HLA-DR induction in the gut and that other soluble factors or agents, alone or interacting with interferon γ, may also be responsible for this event, resulting in the enhanced HLA-DR antigen expression observed in the inflamed intestinal mucosa.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-2568
    Keywords: interferon ; intestinal immunity ; Crohn's disease ; ulcerative colitis ; inflammatory bowel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immune (γ) Interferon is a substance produced by immunologically activated mononuclear cells. Besides its antiviral activity, interferon γ has a crucial role in immunoregulation, by acting directly upon lymphocytes and monocytes, and interacting with other soluble mediators of the immune response. Studies of the interferon system in inflammatory bowel disease have been limited, and little information is available on the generation of interferon during immunological events occurring in the human gut. To investigate the capacity of intestinal mucosal mononuclear cells to produce interferon γ, lamina proprial mononuclear cells, isolated from Crohn's disease, ulcerative colitis, and control patients, were incubated with interleukin 2 or phytohemagglutinin, and the amounts of interferon γ present in the culture supernatants were measured by a virus cytopathic effect inhibition assay. Under identical stimulatory conditions, culture supernatants of cells derived from actively involved mucosa of inflammatory bowel disease specimens contained two- to fivefold less interferon γ than those of cells from control tissue. However, the amount of interferon γ present in supernatants of cells from uninvolved inflammatory bowel disease mucosa was similar to that found in control supernatants. These results indicate that, in patients with active Crohn's disease and ulcerative colitis, mononuclear cells produce decreased amounts of interferon γ in the intestinal mucosa. The exact significance of these findings is unclear, but because of the importance of interferon γ in a variety of cell-mediated immune phenomena, its impaired availability might be relevant to the pathogenesis of inflammatory bowel disease.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 40 (1995), S. 1498-1505 
    ISSN: 1573-2568
    Keywords: ulcerative colitis ; Crohn's disease ; inflammatory bowel disease ; interleukin-1β ; interleukin-2 ; quantitative reverse transcription-polymerase chain reaction ; biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endoscopic biopsies are being increasingly utilized to investigate cytokine profiles in normal and diseased intestine. To evaluate the adequacy of mucosal biopsies as a source of cytokine-specific mRNA, we measured their content of interleukin-1β (IL-1β) and interleukin-2 (IL-2) mRNA by reverse transcription-polymerase chain reaction and compared it to that of autologous lamina propria mononuclear cells in control and inflammatory bowel disease-involved specimens. High-quality total RNA was recovered more consistently from cell isolates than from biopsies. Interleukin-1β mRNA was reliably detected in both cell and biopsy samples, whereas IL-2 mRNA was measurable in all lamina propria cells but not always in biopsies. Compared to controls, levels of IL-1β were significantly elevated in Crohn's disease and ulcerative colitis cells and biopsies, and a weak but significant correlation existed between values derived from the two sources. In contrast, only ulcerative colitis cell isolates but not biopsies contained significantly reduced concentrations of IL-2 mRNA compared to those of control and Crohn's disease samples, and no correlation was found between cell and biopsy contents. Widely different levels of cytokine-specific mRNA were present in closely adjacent biopsies, particularly for IL-2. These results suggest that mucosal biopsies are suitable to assess some but not all cytokine-specific mRNA due to variation in RNA recovery, intrinsic level of cytokine gene expression, and substantial variability of cytokine transcripts.
    Type of Medium: Electronic Resource
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