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

TY - JOUR

T1 - Depigmented-polymerised allergoids favour regulatory over effector T cells

T2 - enhancement by 1α, 25-dihydroxyvitamin D3

AU - Urry, Zoe L

AU - Richards, David F

AU - Black, Cheryl

AU - Morales, Maria

AU - Carnés, Jerónimo

AU - Hawrylowicz, Catherine M

AU - Robinson, Douglas S

PY - 2014/5/29

Y1 - 2014/5/29

N2 - 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 1 alpha, 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. 1 alpha, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.

AB - 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 1 alpha, 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. 1 alpha, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.

KW - Allergens

KW - Animals

KW - Calcitriol

KW - Cytokines

KW - Drug Synergism

KW - Forkhead Transcription Factors

KW - Humans

KW - Hypersensitivity

KW - Immunophenotyping

KW - Interleukin-2 Receptor alpha Subunit

KW - Interleukin-7 Receptor alpha Subunit

KW - Lymphocyte Activation

KW - Phenotype

KW - Plant Extracts

KW - Poaceae

KW - Pollen

KW - Pyroglyphidae

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes, Regulatory

U2 - 10.1186/1471-2172-15-21

DO - 10.1186/1471-2172-15-21

M3 - Article

C2 - 24884430

SN - 1471-2172

VL - 15

JO - BMC Immunology

JF - BMC Immunology

M1 - 21

ER -