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Th1 Cytokine Production (th1 + cytokine_production)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Deficient translocation of c-Rel is associated with impaired Th1 cytokine production in T cells from atopic dermatitis patients

EXPERIMENTAL DERMATOLOGY, Issue 1 2005
Karsten Dieckhoff
Abstract:, Decreased production of T helper type 1 (Th1) cytokines, such as interferon-, (IFN-,) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-, and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-,B) transcription factors , p65 or c-Rel , show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-, and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-,. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-,B-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD. [source]

Crystallization and preliminary X-ray crystallographic studies on the fungal immunomodulatory protein Fve from the golden needle mushroom (Flammulina velutipes)

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2003
See Voon Seow
The fungal immunomodulatory protein from the edible golden needle mushroom (Flammulina velutipes), designated Fve, is a single polypeptide consisting of 114 amino-acid residues. It is believed to trigger the mitogenic proliferation of T lymphocytes and Th1 cytokine production. Here, it is demonstrated that Fve forms a homodimer in nature. In order to understand the relationship between its structure and function, Fve was crystallized using the hanging-drop method; the protein formed well diffracting crystals within 3,5,d in 2.5% PEG 400, 2.0,M ammonium sulfate and 0.1,M Tris base buffer pH 8.5. The space group of the Fve crystals is either P43212 or P41212, with unit-cell parameters a = b = 96.92, c = 61.42,Å. The crystal contains two molecules per asymmetric unit and diffracts to 1.4,Å resolution when exposed to synchrotron radiation. [source]

Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004
M. Caproni
Summary Background, There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes. Objectives, To characterize the immunophenotype of the cells that infiltrate the lesional skin of DM and to evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of specific cytokines, chemokine receptors and markers of cellular activation. Methods, Skin biopsy specimens derived from pathognomonic lesions (Gottron's papules and Gottron's sign) of eight patients with DM were immunostained with a large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO), eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-,, tumour necrosis factor-,, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alkaline phosphatase,antialkaline phosphatase method. Control specimens were obtained from five healthy subjects and from six patients with discoid lupus erythematosus. Results, Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was approximately 2·5. A mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXCR3 were detected. Neutrophil granulocytes were the second most abundant population; eosinophil granulocytes were very poorly represented. Conclusions, Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40L could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation. [source]