The online version of this article (doi:10.1186/1471-2172-15-21) contains supplementary material, which is available to authorized users.
Catherine M Hawrylowicz and Douglas S Robinson contributed equally to this work.
Authors declare no competing financial interests.
CMH and DS conceived and secured funding for the project. ZLU, DFR, CB, MEM, JC, CMH and DSR contributed to the design of, performed and analyzed data from all experiments. ZLU, DSR and CMH designed the study. ZLU, DR and CB performed all experiments. MEM measured serum allergen specific IgE and with JC supervised preparation of extracts. ZLU, DFR, DSR and CMH analysed data and ZLU, DSR and CMH wrote the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
Casanovas M, Gómez MJ, Carnés J, Fernández-Caldas E: Skin tests with native, depigmented and glutaraldehyde polymerized allergen extracts. J Investig Allergol Clin Immunol. 2005, 15: 30-36. PubMed
Garcia-Robaina JC, Sanchez I, de la Torre F, Fernandez-Caldas E, Casanovas M: Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study. J Allergy Clin Immunol. 2006, 118: 1026-1032. 10.1016/j.jaci.2006.07.043. PubMedCrossRef
Lund L, Henmar H, Würtzen PA, Lund G, Hjortskov N, Larsen JN: Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy. Clin Exp Allergy. 2007, 37: 564-71.32. 10.1111/j.1365-2222.2007.02687.x. PubMedCrossRef
Kahlert H, Stuwe H-T, Cromwell O, Fiebig H: Reactivity of T cells with grass pollen allergen extract and allergoid. Int Arch Allergy Immunol. 1999, 120: 146-157. 10.1159/000024233. CrossRef
Chambers ES, Nanzer AM, Richards DF, Ryanna K, Freeman AT, Timms PM, Martineau AR, Griffiths CJ, Corrigan CJ, Hawrylowicz CM: Serum 25-dihydroxyvitamin D levels correlate with CD4 (+) Foxp3 (+) T-cell numbers in moderate/severe asthma. J Allergy Clin Immunol. 2012, 130 (2): 542-544. 10.1016/j.jaci.2012.04.022. PubMedCrossRef
Urry ZL, Chambers ES, Xystrakis E, Dimeloe S, Richards DF, Gabryšová L, Christensen J, Gupta A, Saglani S, Bush A, O'Garra A, Brown Z, Hawrylowicz CM: The role of 1α, 25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells. Eur J Immunol. 2012, 42 (10): 2697-2708. 10.1002/eji.201242370. PubMedPubMedCentralCrossRef
Taher YA, van Esch BC, Hofman GA, Henricks PA, van Oosterhout AJ: 1alpha, 25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol. 2008, 180: 5211-5221. 10.4049/jimmunol.180.8.5211. PubMedCrossRef
Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ, Grönlund H, van Hage M, Reynolds CJ, Boyton RJ, Cobbold SP, Kay AB, Altmann DM, Lloyd CM, Larché M: Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med. 2009, 206 (7): 1535-1547. 10.1084/jem.20082901. PubMedPubMedCentralCrossRef
- Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3
Zoe L Urry
David F Richards
Catherine M Hawrylowicz
Douglas S Robinson
- BioMed Central
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