CD56+ T cells in the peripheral blood of uveitis patients.
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AIMS: Natural killer T (NKT) cells, T lymphocytes expressing both T cell and NK cell markers, are suggested to be involved in autoimmune diseases. To examine the relation between the pathogenesis of uveitis and CD56+ T cells, which are thought to be a type of human NKT cells, we investigated peripheral CD56+ T cells in uveitis patients. METHODS: 41 uveitis patients (Behcet's disease (BD), 14; sarcoidosis (SAR), eight; Vogt-Koyanagi-Harada disease (VKH), five; idiopathic uveitis (IU), nine; and others, five) and 19 healthy controls participated in this study. Cell surface antigens of lymphocytes were analysed by use of monoclonal antibodies and flow cytometry. RESULTS: The proportion of CD56+ T cells in patients with BD was higher than in controls and in patients with SAR, VKH, IU, and others. CONCLUSION: Increased peripheral CD56+ T cells might be relevant to the pathogenesis of uveitis in BD, and increase of peripheral CD56+ T cells may be one of the laboratory findings to suggest that uveitis originates from BD. (+info)
The effect of hormone replacement therapy on the number and the proliferation index of endometrial leukocytes.
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This study aimed to determine the changes in endometrial leukocyte subpopulations under sequential hormone replacement therapy (HRT) during the late progestogenic phase. The number of leukocytes was determined using immunohistochemistry utilizing monoclonal antibodies to CD45 (total leukocytes), CD56 (endometrial granulated lymphocytes), CD3 (T-cells), and CD68 (macrophages). Leukocyte proliferation was demonstrated using in-situ hybridization with a histone probe, and the proliferation index was determined using double labelling for Ki67 (Mib1). Compared to the corresponding phase of the physiological cycle, sequential HRT-treated endometrium exhibited a 95% increase in CD45(+) cells (P < 0.05), a 130% increase in CD56(+) cells (P < 0.05), and a 113% increase in CD3 cells. There was a non-statistically significant drop in the number of CD68(+) cells. The number of proliferating leukocytes increased in sequential HRT endometrium. (+info)
Up-regulation of IL-12 in monocytes: a fundamental defect in common variable immunodeficiency.
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We show that LPS-stimulated circulating CD14-positive monocytes from patients with common variable immunodeficiency (CVID) express a higher proportion of intracellular IL-12-positive cells than monocytes from patients with X-linked agammaglobulinemia or normal subjects. We used four-color flow cytometry and measured IL-12 with an Ab to the p40 subunit following stimulation with LPS. The raised IL-12 is associated with an increased frequency of IFN-gamma-positive T cells, but not of IFN-gamma-positive CD56+ NK cells. These increases in frequency of cytokine-positive cells are due to a decrease in the absolute numbers of circulating monocytes and T cells that are negative for IL-12 and IFN-gamma, respectively. The increased frequency of IL-12-positive monocytes appears to be selective because TNF-alpha was not increased, and is thus unlikely to reflect a general activation. Chronic infection is also unlikely to explain our data since cells from X-linked agammaglobulinemia patients with a similar Ig deficiency do not show these changes. Our data suggest a fundamental abnormality in the IL-12/IFN-gamma circuit in CVID, with up-regulation of IL-12 being the "primary" factor. This imbalance is likely to skew the immune response away from Ab production and also explains the failure of CVID T cells to make Ag-specific memory cells and the chronic inflammatory and granulomatous complications that are a feature of CVID. This disease appears to be a rare example of a polarized Th1-type response and may in part be due to a genetic defect in the control of IL-12 production. (+info)
Functional expression of CD43 on human natural killer cells.
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CD43 is the major leukocyte sialoglyco-protein that plays important functional roles in neutrophils and lymphocytes. However, the expression of CD43 on human natural killer (NK) cells and its participation in the regulation of NK activity has not been studied. We have therefore investigated the expression of CD43 isoforms on human NK cell subpopulations as well as the role of this molecule in NK cell activation and cytotoxicity. We found that CD56bright and CD56dim NK cells express different sialylated forms of CD43, observing that activation of the CD56bright NK cells induces the change of tetrasaccharide O-glycans to hexasaccharide O-glycans on CD43. Cross-linking of the molecule with mAbs results in a metalloprotease-dependent loss of CD43 from the NK cell surface, whereas soluble anti-CD43 mAbs induce a vigorous NK cell proliferation. This property is distinct from T cells, which proliferate after CD43 cross-linking only in the presence of monocytes. Occupancy of the CD43 receptor on NK cells transduces specific signals, leading to enhanced killing activity and tyrosine phosphorylation and de-phosphorylation of several substrates. We therefore propose that CD43 significantly contributes to the regulation of the NK cell function by participating in the control of effector/target interactions and, if pertinent, by transducing activation signals. (+info)
Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia.
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We have investigated the effect of pain without tissue injury on natural killer (NK) cell activity in peripheral blood in humans and the effect of local anaesthesia on the response. Ten subjects were investigated during two sessions. First, self-controlled painful electric stimulation was applied to abdominal skin for 30 min to an intensity of 8 on a visual analogue scale (0-10). Next, the electric intensity profile was reproduced during local anaesthesia (mepivacaine 10 mg ml-1 s.c. to a total dose of 2.5 mg kg-1). NK cell cytotoxicity was measured using a 4-h 51Cr-release assay against K562 target cells. NK cell activity increased from mean 22 (SEM 4)% (baseline) to 35 (6)% and 36 (5)% after 15 and 30 min of painful stimulation, respectively (P < 0.02). A simultaneous increase in the number of CD56+ cells in peripheral blood during pain was found. Stimulation after local anaesthesia did not change either NK cell activity or number. Parallel and significant increases in concentrations of plasma epinephrine and serum cortisol were observed. These changes were abolished by local anaesthesia. We conclude that acute severe pain without tissue injury markedly increased NK cell cytotoxicity. Local anaesthesia completely abolished this immunological and hormonal response. (+info)
Cutting edge: cytolytic effector function in human circulating CD8+ T cells closely correlates with CD56 surface expression.
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Recent data suggest that human effector CD8+ T cells express a distinct CD27-CD45RAhigh (CD57+CD28-CD11ahigh) phenotype. Here, we propose that CTL effector function correlates better with CD56 (neuronal cell adhesion molecule (NCAM)) surface expression. CD56 was absent on cord blood CD8+ T cells, but was expressed by 4-30% of freshly isolated circulating CD8+ T cells from 15 adults. Dramatic oligoclonal expansions in 3/3 individuals were confined to the CD56+ subset of CD8+ T cells. The CD56+ subset generally contained high amounts of intracellular perforin and granzyme B. Finally, direct cytolytic capacity was closely restricted to the CD56+(CD45RAhigh) cells, better than to CD27-CD45RAhigh cells in 5/5 individuals analyzed. Thus, the phenotype corresponding to the circulating effector CD8+ T cell pool may be simplified and more precisely defined by the use of just two surface markers: CD8 and CD56. (+info)
Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y.
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BACKGROUND: Natural killer (NK) cells play a role in natural immunity against tumor and infected cells. Advanced aging is associated with functional impairment of NK cells and increased susceptibility to nutritional deficiencies. OBJECTIVE: Our objective was to test whether micronutrient status affects NK cell activity in an older population. DESIGN: The relations between NK cell variables (percentage of leukocytes and cytotoxicity) and blood concentrations of selected micronutrients were studied in 62 healthy, free-living northern Italian subjects (25 men, 37 women) aged 90-106 y. Anthropometric measurements were also made. RESULTS: All subjects were well nourished according to age-specific anthropometric norms but many of them had micronutrient deficiencies. The prevalence of micronutrient deficiency was highest for selenium (in approximately 50% of both sexes), zinc (in 52% of men and 41% of women), and vitamin B-6 (in 40% of men and 59% of women), followed by vitamin A (in 16% of men and 27% of women) and vitamin E, vitamin B-12, and folate (each in <10% of both sexes). Ubiquinone-10 status was inadequate in 40% of women and 24% of men (P = 0.02). The percentage of NK cells was associated with serum zinc (men: r = 0.573, P = 0. 007; women: r = 0.373, P = 0.031) and selenium (women: r = 0.409, P = 0.018) concentrations. In women only, NK cell cytotoxicity at different effector-target cell ratios was positively associated with plasma vitamin E and ubiquinone-10 concentrations (P < 0.05). No significant associations with NK cell variables were found for the other measured nutrients. CONCLUSIONS: The results of this study strengthen the hypothesis that individual micronutrients may affect the number and function of NK cells in old age. The study also confirms the high prevalence of micronutrient deficiencies in healthy and apparently well-nourished persons aged >/=90 y. (+info)
Angiodestruction and tissue necrosis of skin-involving CD56+ NK/T-cell lymphoma are influenced by expression of cell adhesion molecules and cytotoxic granule and apoptosis-related proteins.
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We compared the expression of cell adhesion molecules (CAMs), cytotoxic granule proteins, and apoptosis-related proteins by immunohistology and in situ terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) of 10 cases of cutaneous CD56+ NK/T cell lymphoma with and 6 cases without angiodestruction. Lymphoma cells in cases with angiodestruction frequently expressed CAMs CD2, CD11a, and CD49d and their ligands CD58, CD54, and CD106 and were positive for CD122 and cytotoxic granule proteins TIA1, perforin, and granzyme B. Lymphoma cells in cases without angiodestruction mostly were negative for CD2, CD58, CD54, CD106, and TIA1 and weakly positive for perforin and granzyme B. In the TUNEL method, mean apoptotic indices (AI) for cases with angiodestruction showed a higher percentage than those without angiodestruction. CD95L, CD95, apoptosis-induced cysteine protease CPP32, apoptosis-promoting protein Bax, and proliferating marker (MIB1) frequently were positive in the lymphoma cells of cases with angiodestruction, but there was no expression of apoptosis-inhibitor protein Bcl2. In most cases without angiodestruction, lymphoma cells were positive for CD95L and Bax and negative for CD95, CPP32, and MIB1. CAMs and the 3 cytotoxic granule proteins and an apoptosis pathway might be important factors in the paracrine and autocrine mechanisms of tissue necrosis in cutaneous CD56+ NK/T cell lymphoma. (+info)