Peptide-mediated immunoregulation.

C Hetzel; G F Hoyne; J R Lamb

doi:10.1159/000237001

Home/Archive/PubMed

PubMed · 7613149

Peptide-mediated immunoregulation.

C Hetzel·G F Hoyne·J R Lamb

View original source ↗Export metadata ↓

Abstract

Quantitative and qualitative characteristics of the signals received by a T cell determine whether receptor ligation results in cell activation, cell death, or the induction of antigen-specific non-responsiveness. Environmental factors such as the nature of costimulation, antigen-presenting cell type, peptide structure and cytokine levels also influence the differentiation of CD4+ helper T cells into functionally distinct subsets, which now appear pivotal in many immune-mediated disorders, including autoimmunity and allergy. Selective manipulation of the immune response, such as the functional inactivation or deviation of the cytokine secretion patterns of specific T cells, may be an effective strategy for immunotherapy.

Explore related subjects

Allergens Animals Antigen Presentation Cats Cytokines Desensitization, Immunologic Glycoproteins Humans Hypersensitivity Immune Tolerance Mice Peptide Fragments Th1 Cells Th2 Cells Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

C Hetzel, G F Hoyne, J R Lamb. Peptide-mediated immunoregulation.. https://doi.org/10.1159/000237001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1997

Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and restricted V beta repertoire in nickel-mediated contact dermatitis.

In this study we compared the phenotype and cytokine patterns of nickel-specific T cell clones (TCC) derived from blood samples and positive patch test reactions. A total of 252 nickel-specific TCC were established from three nonatopic patients with allergic contact dermatitis caused by nickel. All TCC expressed the TCR-alpha beta, and 77% were CD4+ compared with 21% CD8+ TCC. In contrast to blood-derived TCC, the majority of skin-derived CD4+ or CD8+ T lymphocytes produced IL-4 either in combination with IFN-gamma (type 0 cytokine pattern) or IL-4 exclusively (type 2 pattern). Skin-derived nickel-specific TCC of each patient secreted significantly more IL-4 than blood-derived TCC of the same individual. Analysis of TCR-V beta repertoire from two patients indicated that >40% of the tested TCC expressed one of the following V beta elements: V beta 13.1/13.2, V beta 20, V beta 2, V beta 6.7, or V beta 14. Only 20% of unstimulated T cells but >40% of nickel-stimulated T cells derived from peripheral blood of the same individuals expressed these V beta elements, suggesting a selection of certain TCR-V beta elements by nickel sulfate in these patients. In contrast to the compartmentalization of IL-4 production, there were no major differences in the expression of TCR-V beta elements between blood- and skin-derived nickel-specific TCC. These results point to a modulation of the cytokine production pattern of T lymphocytes after their migration from peripheral blood into the skin and a production of the type 2 cytokine IL-4 in acute eczematous lesions in nonatopic individuals.

Allergens↗

PubMed1997

Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma.

In patients with asthma, elevations of IgE correlate both with allergic inflammation of the airways and with bronchial hyperreactivity (BHR). Several investigations, using mouse models of this disease, have indicated a central role for IgE in the pathogenesis of the eosinophilic inflammation as well as in the obstructive airway physiology of BHR. Some diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a null mutation of the C epsilon locus to show that bronchial inflammation and BHR in response to allergen inhalation both can occur in the absence of IgE. We demonstrate that the eosinophilic bronchial inflammation elicited in an established mouse model of hypersensitivity to Aspergillus fumigatus (Af) is accompanied by the asthmatic physiology of BHR. Wild-type and IgE-deficient mice were sensitized intranasally with Af extract. Both groups of animals developed bronchoalveolar lavage eosinophilia and pulmonary parenchymal eosinophilia. This was accompanied by increased serum levels of total and Af-specific IgE in the wild-type animals only. This Af-sensitization protocol resulted in significant BHR in both wild-type mice and IgE-deficient mice. Interestingly, unsensitized IgE-deficient mice had increased bronchial responsiveness compared with unsensitized wild-type controls. We conclude that BHR and airways inflammation can be fully expressed via IgE-independent mechanisms. These may involve the activation of mast cells by factors other than IgE as well as a mucosal lymphocyte-mediated immune response to allergen.

Allergens↗

PubMed1997

Molecular cloning and immunological characterisation of Cyn d 7, a novel calcium-binding allergen from Bermuda grass pollen.

A cDNA coding for a newly identified Bermuda grass pollen allergen, Cyn d 7, with significant sequence similarity to Ca2+-binding proteins, was isolated from a cDNA expression library using serum IgE from an allergic individual. The deduced amino acid sequence of Cyn d 7 contained two typical Ca2+-binding sites (EF hand domains). Depletion of Ca2+ with EGTA led to a loss of IgE-binding capacity of rCyn d 7. A synthetic peptide based on domain II showed high IgE reactivity. Cyn d 7 therefore represents a grass pollen allergen that belongs to a novel class of Ca2+-binding proteins.

Allergens↗