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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Immunology 1/2014

Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3

Zeitschrift:
BMC Immunology > Ausgabe 1/2014
Autoren:
Zoe L Urry, David F Richards, Cheryl Black, Maria Morales, Jerónimo Carnés, Catherine M Hawrylowicz, Douglas S Robinson
Wichtige Hinweise

Electronic supplementary material

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.

Competing interests

Authors declare no competing financial interests.

Authors’ contributions

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.

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.
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