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Biomedical subjects

H U Simon

Publications and source records attributed to H U Simon.

98 records · Page 6Linked to original sources
PubMedDate not supplied

Regulation of allergic inflammation by skin-homing T cells in allergic eczema.

BACKGROUND: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte-associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin-related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. METHODS: CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of AD patients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. RESULTS: The CLA+ CD45RO+ T cells represent an in- vivo-activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL-5 and IL-13 but only very little IL-4 and IFN-gamma in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA- population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. CONCLUSION: Our results indicate that in-vivo-activated both CD4+ and CD8+ memory/effector T cells with skin-homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions.

Animals↗
PubMedDate not supplied

Clinical and immunological features of patients with interleukin-5-producing T cell clones and eosinophilia.

Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients.

Clone Cells↗
PubMedDate not supplied

Human peripheral blood eosinophils express and release interleukin-8.

Eosinophils can synthesize various cytokines. We demonstrate that interleukin-8 (IL-8) mRNA and protein are constitutively expressed by freshly isolated resting human eosinophils. Most of the patients with bronchial asthma or atopic dermatitis show evidence for up-regulated IL-8 protein expression in eosinophils but not in neutrophils, suggesting that an eosinophil-specific cytokine may act in these patients. To investigate whether the intracellular IL-8 can be released, eosinophils were stimulated by different cytokines and platelet-activating factor (PAF). Priming with granulocyte/macrophage-colory-stimulating factor and a subsequent 25-min stimulation with RANTES or PAF resulted in release of IL-8 from highly purified human eosinophils in vitro.

Asthma↗
PubMedDate not supplied

Molecular mechanisms of defective eosinophil apoptosis in diseases associated with eosinophilia.

Apoptosis is a necessary process to maintain correct cell numbers in a multicellular organism. Defects in this process may contribute to the pathogenesis of a number of human diseases. We have suggested that inhibition of apoptosis in eosinophils by cytokines such as IL-5 and GM-CSF may play an important role in the pathogenesis of allergic disorders. Here, we review our recent progress in understanding the processes regulating eosinophil apoptosis.

Apoptosis↗
PubMedDate not supplied

Clinical, biochemical and immunological effectiveness of diacetyl-splenopentin (BCH 069) in hay fever.

Diacetyl-splenopentin (BCH 069) is a new pentapeptide of splenin modified by twofold acetylation. BCH 069 has thymopentin-like activity demonstrated by in vivo animal and in vitro human studies. Two groups of patients received 50 mg BCH 069 and placebo, respectively, by subcutaneous injection 3 times weekly for 4 weeks. The third group of patients received 50 mg BCH 069 by intravenous injection 3 times weekly for 6 weeks. The therapy was carried out during the peak of the pollen season. BCH 069 intravenous treatment was found to be significantly superior to placebo treatment in reducing clinical symptoms. Biochemical inflammatory signs were not observed. No increase of bronchomotoric reactivity was established in comparison to the placebo group. There was a significantly lower increase in gras-spollen specific IgE and IgG4 in the intravenous group of BCH 069. Subcutaneous therapy with BCH 069 was not effective. The study demonstrated that BCH 069 used intravenously induces clinical improvement in patients suffering from hay fever. Thus the possibility to influence hyperreactive conditions of the immune system has been confirmed. The study indicates that various application routes of BCH 069 have different effects on the immune system.

Humans↗
PubMedDate not supplied

P-glycoprotein expression in circulating blood leukocytes of patients with steroid-resistant asthma.

P-Glycoprotein is a transmembrane efflux pump for different lipophilic drugs including glucocorticosteroids. Thus, upregulation of P-glycoprotein may provide a mechanism for reduced glucocorticosteroid responses as they occur in steroid-resistant asthma. To address this issue, we have examined freshly isolated peripheral blood mononuclear cells and granulocytes with regards to P-glycoprotein functional and surface expression. Using two-color immuno fluorescence techniques, we demonstrated a direct correlation between the efflux of the fluorescent dye Rh 123 and P-glycoprotein surface expression in lymphocytes, NK (natural killer) cells, monocytes and granulocytes. P-Glycoprotein levels varied widely between different leucocytes, with NK cells and CD8+ T cells having high, and granulocytes having no detectable levels. There was no evidence for upregulation of P-glycoprotein expression in any cell type from patients with steroid-resistant asthma compared to patients with steroid-sensitive or mild asthma. These results suggest that increased P-glycoprotein expression can be excluded as a mechanism for steroid resistance. Interestingly, a down regulation of P-glycoprotein expression in B cells was associated with systemic glucocorticosteroid treatment in vivo and in vitro. Whether this phenomenon may account for reduced immunoglobulin levels associated with oral glucocortico-steroid therapy remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗