title: Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3.
abstract: BACKGROUND
  Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy. Effective SIT is thought to act through regulatory T cells (Tregs) rather than activation of effector T cells. There is no published data on the activity of modified extracts on Tregs.
  
  
  RESULTS
  We compared the capacity of modified (depigmented-polymerised) versus unmodified (native) allergen extracts of grass pollen and house dust mite to stimulate proliferation/cytokine production and to modulate Treg/effector T cell frequency in cultures of peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both allergens in vitro. Depigmented-polymerised allergen extracts stimulated less proliferation of PBMC, and reduced effector cell numbers after 7 days in culture than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were similar to those seen with native extract so that ratios of regulatory to effector T cells were significantly increased in cultures stimulated with depigmented-polymerised extracts. Addition of 1α, 25-dihydroxyvitamin D3 further favoured Treg, and reduced effector cytokine production, but not interleukin-10.
  
  
  CONCLUSIONS
  Depigmented-polymerised allergen extracts appear to favour Treg expansion over activation of effector T cells and this may relate to their demonstrated efficacy and safety in SIT. 1α, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.
authors.forename: Zoe L
authors.initials: ZL
authors.lastname: Urry
authors.forename: David F
authors.initials: DF
authors.lastname: Richards
authors.forename: Cheryl
authors.initials: C
authors.lastname: Black
authors.forename: Maria
authors.initials: M
authors.lastname: Morales
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Carnés
authors.affiliation: Department of Allergy and Asthma, MRC and Asthma UK Centre for Mechanisms of Allergic Asthma, Guy's Campus, King's College London, London, UK. catherine.hawrylowicz@kcl.ac.uk.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Robinson
mesh_terms: D000485:Allergens / Q000276:immunology; D000080384:Allergoids; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D010936:Plant Extracts / Q000494:pharmacology*; D006109:Poaceae / Q000009:adverse effects; D011058:Pollen / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000080384:Allergoids; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D010936:Plant Extracts; D002117:Calcitriol