Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants

Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro‐allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non‐microbial stimuli in infants at high risk of allergic disease an...

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Main Authors: Ismail, Intan Hakimah, Boyle, Robert J., Li, Jeen Mah, Licciardi, Paul V., Tang, Mimi L. K.
Format: Article
Language:English
Published: Wiley 2015
Online Access:http://psasir.upm.edu.my/id/eprint/46104/1/Reduced%20neonatal%20regulatory%20T%20cell%20response%20to%20microbial%20stimuli%20associates%20with%20subsequent%20eczema%20in%20high%20risk%20infants.pdf
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author Ismail, Intan Hakimah
Boyle, Robert J.
Li, Jeen Mah
Licciardi, Paul V.
Tang, Mimi L. K.
author_facet Ismail, Intan Hakimah
Boyle, Robert J.
Li, Jeen Mah
Licciardi, Paul V.
Tang, Mimi L. K.
author_sort Ismail, Intan Hakimah
collection UPM
description Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro‐allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non‐microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year. Methods: Cord blood mononuclear cells from 72 neonates were cultured with toll‐like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat‐killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti‐CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization). Results: Infants with eczema (n = 24) had reduced percentages of FoxP3hiCD25hi Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL‐10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti‐CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non‐sensitized infants. Conclusions: High‐risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy.
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spelling upm.eprints-461042018-05-07T01:41:46Z http://psasir.upm.edu.my/id/eprint/46104/ Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants Ismail, Intan Hakimah Boyle, Robert J. Li, Jeen Mah Licciardi, Paul V. Tang, Mimi L. K. Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro‐allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non‐microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year. Methods: Cord blood mononuclear cells from 72 neonates were cultured with toll‐like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat‐killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti‐CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization). Results: Infants with eczema (n = 24) had reduced percentages of FoxP3hiCD25hi Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL‐10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti‐CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non‐sensitized infants. Conclusions: High‐risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy. Wiley 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/46104/1/Reduced%20neonatal%20regulatory%20T%20cell%20response%20to%20microbial%20stimuli%20associates%20with%20subsequent%20eczema%20in%20high%20risk%20infants.pdf Ismail, Intan Hakimah and Boyle, Robert J. and Li, Jeen Mah and Licciardi, Paul V. and Tang, Mimi L. K. (2015) Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants. Pediatric Allergy and Immunology, 25 (7). pp. 674-684. ISSN 0905-6157; ESSN: 1399-3038 http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1399-3038 10.1111/pai.12303
spellingShingle Ismail, Intan Hakimah
Boyle, Robert J.
Li, Jeen Mah
Licciardi, Paul V.
Tang, Mimi L. K.
Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title_full Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title_fullStr Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title_full_unstemmed Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title_short Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants
title_sort reduced neonatal regulatory t cell response to microbial stimuli associates with subsequent eczema in high risk infants
url http://psasir.upm.edu.my/id/eprint/46104/1/Reduced%20neonatal%20regulatory%20T%20cell%20response%20to%20microbial%20stimuli%20associates%20with%20subsequent%20eczema%20in%20high%20risk%20infants.pdf
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