Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure

Thanh D. Dang, Katrina J. Allen, David J. Martino, Jennifer J. Koplin, Paul V. Licciardi, Mimi L K Tang

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. 

Objectives: To examine changes in peripheral blood CD4+CD25+Foxp3+ Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. 

Methods: A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. 

Results: Non-allergic infants showed stable total Treg frequencies over time; food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6); and food-allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). 

Conclusion: Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction. 

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalPediatric Allergy and Immunology
Volume27
Issue number1
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

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Infant Food
Regulatory T-Lymphocytes
Allergens
Food
Ovum
Hypersensitivity
Egg Hypersensitivity
Peanut Hypersensitivity
Food Hypersensitivity
Population
T-Lymphocytes

Cite this

Dang, T. D., Allen, K. J., J. Martino, D., Koplin, J. J., Licciardi, P. V., & Tang, M. L. K. (2016). Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure. Pediatric Allergy and Immunology, 27(1), 35-43. https://doi.org/10.1111/pai.12498
Dang, Thanh D. ; Allen, Katrina J. ; J. Martino, David ; Koplin, Jennifer J. ; Licciardi, Paul V. ; Tang, Mimi L K. / Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure. In: Pediatric Allergy and Immunology. 2016 ; Vol. 27, No. 1. pp. 35-43.
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title = "Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure",
abstract = "Background: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. Objectives: To examine changes in peripheral blood CD4+CD25+Foxp3+ Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. Methods: A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. Results: Non-allergic infants showed stable total Treg frequencies over time; food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87{\%} day 0, 5.27{\%} day 2, 6.5{\%} day 6); and food-allergic infants showed persistent reduction in Treg (6.85{\%} day 0, 5.4{\%} day 2, 6.2{\%} day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). Conclusion: Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction. ",
keywords = "Egg allergy, Food allergy, FoxP3, HealthNuts, Oral food challenge, Peanut allergy, Regulatory T cells, Treg",
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Dang, TD, Allen, KJ, J. Martino, D, Koplin, JJ, Licciardi, PV & Tang, MLK 2016, 'Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure', Pediatric Allergy and Immunology, vol. 27, no. 1, pp. 35-43. https://doi.org/10.1111/pai.12498

Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure. / Dang, Thanh D.; Allen, Katrina J.; J. Martino, David; Koplin, Jennifer J.; Licciardi, Paul V.; Tang, Mimi L K.

In: Pediatric Allergy and Immunology, Vol. 27, No. 1, 01.02.2016, p. 35-43.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure

AU - Dang, Thanh D.

AU - Allen, Katrina J.

AU - J. Martino, David

AU - Koplin, Jennifer J.

AU - Licciardi, Paul V.

AU - Tang, Mimi L K

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. Objectives: To examine changes in peripheral blood CD4+CD25+Foxp3+ Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. Methods: A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. Results: Non-allergic infants showed stable total Treg frequencies over time; food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6); and food-allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). Conclusion: Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction. 

AB - Background: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. Objectives: To examine changes in peripheral blood CD4+CD25+Foxp3+ Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. Methods: A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. Results: Non-allergic infants showed stable total Treg frequencies over time; food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6); and food-allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). Conclusion: Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction. 

KW - Egg allergy

KW - Food allergy

KW - FoxP3

KW - HealthNuts

KW - Oral food challenge

KW - Peanut allergy

KW - Regulatory T cells

KW - Treg

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U2 - 10.1111/pai.12498

DO - 10.1111/pai.12498

M3 - Article

VL - 27

SP - 35

EP - 43

JO - Pediatric Allergy and Immunology

JF - Pediatric Allergy and Immunology

SN - 0905-6157

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