ArticlePloS one2010
Tracking antigen-specific T-cells during clinical tolerance induction in humans.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Hymenoptera venom allergy in children.Italian journal of pediatrics · 2024Review
- Potential and limitations of epitope mapping and molecular targeting in Hymenoptera venom allergy.Frontiers in allergy · 2023Review
- B cells modulate mouse allergen-specific T cells in nonallergic laboratory animal-care workers.JCI insight · 2021Article
- Antigen-specific regulatory T-cell responses against aeroantigens and their role in allergy.Mucosal immunology · 2018Review
- New modalities of allergen immunotherapy.Human vaccines & immunotherapeutics · 2018Article
- Deciphering the black box of food allergy mechanisms.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2017Review
- Pathogenesis of cerebral palsy through the prism of immune regulation of nervous tissue homeostasis: literature review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2016Review
- Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2016Article
- Molecular and cellular mechanisms of food allergy and food tolerance.The Journal of allergy and clinical immunology · 2016Review
- Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- T Cell Epitope Peptide Therapy for Allergic Diseases.Current allergy and asthma reports · 2016Review
- Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals.European journal of immunology · 2016Article
- Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2015Review
- Bee venom processes human skin lipids for presentation by CD1a.The Journal of experimental medicine · 2015Article
- Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens.The World Allergy Organization journal · 2015Article
- Mechanisms of immune tolerance to allergens in children.Korean journal of pediatrics · 2013Review
- Novel developments in the mechanisms of immune tolerance to allergens.Human vaccines & immunotherapeutics · 2012Review
- Immunological mechanisms for desensitization and tolerance in food allergy.Seminars in immunopathology · 2012Review
- Therapies for allergic inflammation: refining strategies to induce tolerance.Nature medicine · 2012Review
- Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab.Mucosal immunology · 2012Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3-5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets.
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Registered trials
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