Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.65 (Der p 1)
 346 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been previously demonstrated that hybrid Ty virus-like particles (VLP) prime effective CD8(+) and CD4(+) T cell responses. In this study, we investigated the effect of treating mice with Ty VLP carrying the immunodominant epitope of Der p 1 after sensitizing them to the group 1 allergen of the house dust mite Dermatophagoides pteronyssinus (Der p 1), under conditions that induce T(h)2 immunity. We show that i.p. treatment with the hybrid VLP abrogated allergen-specific IL-5 production and reduced allergen-specific cell proliferation. This suppression of the response was mediated by CD4(+) T cells and was not accompanied by an increase in IFN-gamma production.
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PMID:CD4(+) T cells induced by virus-like particles expressing a major T cell epitope down-regulate IL-5 production in an ongoing immune response to Der p 1 independently of IFN-gamma production. 1059 Feb 58

The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE antibody responses in a significant proportion of patients suffering from dust mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell surface molecule involved in the homeostatic control of human IgE synthesis, namely the IL-2 receptor (CD25) on T cells. As a result, these T cells show markedly diminished proliferation and IFN-gamma secretion in response to stimulation by anti-CD3 antibody. However, these observations still leave open the important issue of whether CD25 cleavage, and the consequent suppression of IFN-gamma secretion, leads to enhanced IL-4 secretion, and whether such cytokine changes would be exhibited by both CD4 and CD8 T cells. Here we demonstrate for the first time that the proteolytic activity of Der p 1 biases human CD4 and CD8 T cells towards a type 2 cytokine profile. Our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.
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PMID:Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-gamma. 1129 46

Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8(+) T cell epitopes. Using human leukocyte antigen-A*0201-peptide (HLA-A*0201-peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1-specific CD8(+) T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-gamma efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8(+) T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8(+) T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.
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PMID:Allergen-specific CD8(+) T cells and atopic disease. 1241 67

This study investigated the influence of prenatal exposure to house dust mite (HDM, D. pteronyssinus) on interleukin (IL)-2, interferon-gamma (IFN-gamma) and IL-4 producing CD4(+) and CD8(+) T lymphocytes in cord blood as well as on the development of sensitization and occurrence of atopic dermatitis (AD) as the first symptom of allergy during the first year of life. Dust samples (n = 22) were collected by vacuum cleaning the maternal mattress during early to mid-pregnancy. In these samples, the amount of the major HDM antigen (Der p 1) was assessed by a sensitive enzyme-linked immunosorbent assay technique (detection limit 0.004 microg/g dust). Flow cytometry was used to determine cord blood lymphocyte subtypes and to quantify the intracellular amounts of IL-2, IFN-gamma and IL-4 produced by cord blood CD4(+) helper and CD8(+) cytotoxic T lymphocytes, both spontaneously and after stimulation with phorbol-12-mirystate-13-acetate and ionomycin. Children were followed for 1 yr for the presence of symptoms associated with allergy. In addition, at the age of 1 yr specific IgE to different classical inhalant and food allergens was measured. Higher prenatal exposure to Der p 1 (>0.2 microg/g dust) was associated with a significant lower percentage of IFN-gamma producing stimulated CD4(+) T lymphocytes, compared with lower prenatal Der p 1 exposure (p = 0.03). The presence of AD during the first year of life (n = 9) was associated with an increased number of naive CD4(+) CD45RA(+) lymphocytes (p = 0.03), with an increased spontaneous IL-4 production by CD8(+) lymphocytes (p = 0.04) and with a decreased percentage of IFN-gamma producing stimulated CD4(+) lymphocytes (p = 0.04). Furthermore, exposure to HDM during pregnancy tended to be higher in mothers of children with AD during the first year of life when compared with those without AD (p = 0.08). This study shows that the level of prenatal exposure to Der p 1 influences the immune profile of cord blood T lymphocytes and the clinical outcome in early life. Therefore, the prenatal environment must be regarded as a possible early risk factors for allergic diseases in children.
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PMID:Prenatal exposure to house dust mite allergen (Der p 1), cord blood T cell phenotype and cytokine production and atopic dermatitis during the first year of life. 1530 39