Characterization of T Cell Responses to Hev b 3, an Allergen Associated with Latex Allergy in Spina Bifida Patients

Bohle, Barbara; Wagner, B.J.; Vollmann, Ute; Buck, Dietke; Niggemann, B.; Szépfalusi, Zsolt; Fischer, Gottfried; Scheiner, Otto; Breiteneder, Heimo; Ebner, Christof

doi:10.4049/jimmunol.164.8.4393

Cited by 40 publications

(25 citation statements)

References 41 publications

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“…exposure of the skin to protein Ags is a highly skewed Th2 response (34,43,44). Likewise, contact-induced responses to protein Ags in humans, including latex hypersensitivity reactions and contact urticaria, also involve Th2 generation (45)(46)(47)(48). Given that the vast majority of children with atopic dermatitis eventually develop some form of allergic airway disease, it is plausible that penetration of environmental allergens through the skin could serve as a major mode of systemic Th2 sensitization in atopic individuals.…”

Section: Discussionmentioning

confidence: 99%

IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

Herrick

McKenzie

et al. 2003

The Journal of Immunology

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Th2 responses are clearly involved in the pathogenesis of atopic disease. Thus, understanding the factors responsible for Th2 sensitization at sites of allergen exposure, such as airway and skin, is crucial for directing therapeutic or preventive strategies. Contrary to other models of Th2 sensitization to proteins, we have reported that Th2 responses induced by epicutaneous exposure to OVA are IL-4 independent. Combined deficiency of both IL-4 and IL-13 signaling did prevent Th2 generation, suggesting that IL-13 was mediating these IL-4-independent responses. It was not clear, however, whether IL-13 was simply replacing the need for IL-4 in genetically deficient mice or if IL-13 played a unique role. In the present study, we show that Th2 responses induced by epicutaneous OVA exposure (including lung inflammatory responses after inhaled Ag challenge, OVA-specific IgG1, and draining lymph node IL-5 production) are impaired in IL-13-deficient (IL-13−/−) mice compared with wild type. In contrast, i.p. sensitization of IL-13−/− mice resulted in responses equivalent to wild type. Generation of contact hypersensitivity to dinitrofluorobenzene, which involves Th1 and CD8+ effector cells, was also intact in IL-13−/− mice. Taken together, the data indicate that IL-13 is the major inducer of Th2 generation in the cutaneous microenvironment, being required independently of IL-4. This fact, in combination with the known abundance of IL-13 in atopic dermatitis skin lesions, emphasizes the potentially important role of the skin as a site for Th2 sensitization to environmental allergens, particularly in atopic individuals.

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Section: Discussionmentioning

confidence: 99%

IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

Herrick

McKenzie

et al. 2003

The Journal of Immunology

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“…T cell responses to several allergens have been characterized thoroughly, indicating that allergen-specific Th2 lymphocytes play a predominant role in these diseases, since cytokines produced by this T cell subset (IL-4, IL-13) are potent IgE-switching factors (1)(2)(3)(4). Specific immunotherapy (SIT) 3 proved to be an efficient treatment for patients suffering from type I allergy to airborne allergens (5).…”

Section: Oligodeoxynucleotides Containing Cpg Motifs Induce Low Levelmentioning

confidence: 99%

Oligodeoxynucleotides Containing CpG Motifs Induce Low Levels of TNF-α in Human B Lymphocytes: Possible Adjuvants for Th1 Responses

Bohle

Orel

Ebner

2001

The Journal of Immunology

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Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential adjuvants for specific immunotherapy of type I allergies because they foster Th1-like immune responses. However, previous work has shown that CpG-ODN induce systemically active levels of TNF-α in murine macrophages. The goal of the present study was to evaluate the release of TNF-α in human cells by a CpG-ODN proven to induce Th1 immune responses in cells from atopic individuals and in mice. CpG-ODN induced TNF-α in cells from atopic and healthy individuals. However, the amounts were low, as determined by comparison with commonly used Ags. Intracellular cytokine staining of PBMC revealed that CpG-ODN-induced TNF-α derived exclusively from B lymphocytes. TNF-α contributed to the CpG-ODN-augmented proliferation and Ig synthesis in PBMC, but was not involved in IFN-γ synthesis. In conclusion, our findings indicate that certain CpG-ODN induce low amounts of TNF-α in human B lymphocytes and may therefore be used to modulate Th2-biased immune responses in allergic patients.

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“…Bet v 1 and Mal d 1 share approximately 64.5% sequence identity, with the cross-reacting T cell-reactive peptide fragments sharing 50% sequence identity. However, other studies have not demonstrated T cell cross-reactivity between allergens with a similar degree of sequence identity, as was the case for the major latex allergens, Hev b 1 and Hev b 3, despite 47% sequence identity [29]. In light of these studies, and given that single amino acid substitutions can lead to loss of T cell reactivity [30,31,32], it is likely that shared key amino acid motifs are more important for T cell cross-reactivity than whole epitope sequences.…”

Section: Discussionmentioning

confidence: 99%

Clinical Allergy to Hazelnut and Peanut: Identification of T Cell Cross-Reactive Allergens

Glaspole

León

Prickett

et al. 2011

Int Arch Allergy Immunol

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Background: Peanut and tree nut allergies are life-threatening conditions for many affected individuals worldwide. Currently there is no cure. While co-allergy to peanut and tree nuts is a common clinical observation, and IgE cross-reactivity between peanut and tree nuts is reported, T cell cross-reactivity is poorly defined. Methods: Hazelnut-specific T cell lines were established using peripheral blood mononuclear cells from 5 subjects with co-allergy to hazelnut and peanut. These lines were stimulated with hazelnut and peanut extracts and purified major peanut allergens, Ara h 1 and Ara h 2. Proliferation was determined by ³H-thymidine incorporation and secretion of key Th1 (IFN-γ) and Th2 (IL-5) cytokines analysed by ELISA. Results: Hazelnut-specific T cell lines from all 5 subjects proliferated upon stimulation with both hazelnut and peanut extracts and for 4 subjects, to Ara h 1 and/or Ara h 2. Proliferating cells were mainly CD4+ T cells and produced both IL-5 and IFN-γ in response to hazelnut and peanut stimulation. Mitogenicity of extracts and allergens was excluded by their lack of stimulation of house dust mite-specific T cells. Conclusion: Our finding that hazelnut and peanut co-allergy is associated with cross-reactive T cell responses, driven partly by cross-reactivity to the major peanut allergens Ara h 1 and Ara h 2, points to future development of allergen immunotherapy by targeting cross-reactive T cells.

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Characterization of T Cell Responses to Hev b 3, an Allergen Associated with Latex Allergy in Spina Bifida Patients

Cited by 40 publications

References 41 publications

IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen

Oligodeoxynucleotides Containing CpG Motifs Induce Low Levels of TNF-α in Human B Lymphocytes: Possible Adjuvants for Th1 Responses

Clinical Allergy to Hazelnut and Peanut: Identification of T Cell Cross-Reactive Allergens

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