Changes in Treg and Breg cells in a healthy pediatric population

The interpretation of clinical diagnostic results in suspected inborn errors of immunity, including Tregopathies, is hampered by the lack of age-stratified reference values for regulatory T cells (Treg) in the pediatric population and a consensus on which Treg immunophenotype to use. Regulatory B ce...

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Main Authors: Yiyi Luo, Daniel Acevedo, Alexandru Vlagea, Anna Codina, Ana García-García, Angela Deyà-Martínez, Celia Martí-Castellote, Ana Esteve-Solé, Laia Alsina
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1283981/full
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author Yiyi Luo
Yiyi Luo
Yiyi Luo
Daniel Acevedo
Daniel Acevedo
Daniel Acevedo
Alexandru Vlagea
Alexandru Vlagea
Anna Codina
Ana García-García
Ana García-García
Ana García-García
Angela Deyà-Martínez
Angela Deyà-Martínez
Angela Deyà-Martínez
Celia Martí-Castellote
Celia Martí-Castellote
Celia Martí-Castellote
Ana Esteve-Solé
Ana Esteve-Solé
Ana Esteve-Solé
Laia Alsina
Laia Alsina
Laia Alsina
Laia Alsina
author_facet Yiyi Luo
Yiyi Luo
Yiyi Luo
Daniel Acevedo
Daniel Acevedo
Daniel Acevedo
Alexandru Vlagea
Alexandru Vlagea
Anna Codina
Ana García-García
Ana García-García
Ana García-García
Angela Deyà-Martínez
Angela Deyà-Martínez
Angela Deyà-Martínez
Celia Martí-Castellote
Celia Martí-Castellote
Celia Martí-Castellote
Ana Esteve-Solé
Ana Esteve-Solé
Ana Esteve-Solé
Laia Alsina
Laia Alsina
Laia Alsina
Laia Alsina
author_sort Yiyi Luo
collection DOAJ
description The interpretation of clinical diagnostic results in suspected inborn errors of immunity, including Tregopathies, is hampered by the lack of age-stratified reference values for regulatory T cells (Treg) in the pediatric population and a consensus on which Treg immunophenotype to use. Regulatory B cells (Breg) are an important component of the regulatory system that have been poorly studied in the pediatric population. We analyzed (1) the correlation between the three immunophenotypic definitions of Treg (CD4+CD25hiCD127low, CD4+CD25hiCD127lowFoxP3+, CD4+CD25hiFoxP3+), and with CD4+CD25hi and (2) the changes in Treg and Breg frequencies and their maturation status with age. We performed peripheral blood immunophenotyping of Treg and Breg (CD19+CD24hiCD38hi) by flow cytometry in 55 healthy pediatric controls. We observed that Treg numbers varied depending on the definition used, and the frequency ranged between 3.3–9.7% for CD4+CD25hiCD127low, 0.07-1.6% for CD4+CD25hiCD127lowFoxP3+, and 0.24-2.83% for CD4+CD25hiFoxP3+. The correlation between the three definitions of Treg was positive for most age ranges, especially between the two intracellular panels and with CD4+CD25hi vs CD4+CD25hiCD127low. Treg and Breg frequencies tended to decline after 7 and 3 years onwards, respectively. Treg’s maturation status increased with age, with a decline of naïve Treg and an increase in memory/effector Treg from age 7 onwards. Memory Breg increased progressively from age 3 onwards. In conclusion, the number of Treg frequencies spans a wide range depending on the immunophenotypic definition used despite a good level of correlation exists between them. The decline in numbers and maturation process with age occurs earlier in Breg than in Treg.
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spelling doaj.art-08d8f168c19d4f759226fad154d955732023-11-24T11:07:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12839811283981Changes in Treg and Breg cells in a healthy pediatric populationYiyi Luo0Yiyi Luo1Yiyi Luo2Daniel Acevedo3Daniel Acevedo4Daniel Acevedo5Alexandru Vlagea6Alexandru Vlagea7Anna Codina8Ana García-García9Ana García-García10Ana García-García11Angela Deyà-Martínez12Angela Deyà-Martínez13Angela Deyà-Martínez14Celia Martí-Castellote15Celia Martí-Castellote16Celia Martí-Castellote17Ana Esteve-Solé18Ana Esteve-Solé19Ana Esteve-Solé20Laia Alsina21Laia Alsina22Laia Alsina23Laia Alsina24Clinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainBiomedic Diagnostic Center (CDB), Hospital Clínic of Barcelona, Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic de Barcelona, Barcelona, SpainBiobanco Pediátrico para la Investigación Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainClinical Immunology and Primary Immunodeficiencies Unit, Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, SpainClinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, SpainStudy Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Déu, Barcelona, SpainDepartment of Surgery and Medical Specializations, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, SpainThe interpretation of clinical diagnostic results in suspected inborn errors of immunity, including Tregopathies, is hampered by the lack of age-stratified reference values for regulatory T cells (Treg) in the pediatric population and a consensus on which Treg immunophenotype to use. Regulatory B cells (Breg) are an important component of the regulatory system that have been poorly studied in the pediatric population. We analyzed (1) the correlation between the three immunophenotypic definitions of Treg (CD4+CD25hiCD127low, CD4+CD25hiCD127lowFoxP3+, CD4+CD25hiFoxP3+), and with CD4+CD25hi and (2) the changes in Treg and Breg frequencies and their maturation status with age. We performed peripheral blood immunophenotyping of Treg and Breg (CD19+CD24hiCD38hi) by flow cytometry in 55 healthy pediatric controls. We observed that Treg numbers varied depending on the definition used, and the frequency ranged between 3.3–9.7% for CD4+CD25hiCD127low, 0.07-1.6% for CD4+CD25hiCD127lowFoxP3+, and 0.24-2.83% for CD4+CD25hiFoxP3+. The correlation between the three definitions of Treg was positive for most age ranges, especially between the two intracellular panels and with CD4+CD25hi vs CD4+CD25hiCD127low. Treg and Breg frequencies tended to decline after 7 and 3 years onwards, respectively. Treg’s maturation status increased with age, with a decline of naïve Treg and an increase in memory/effector Treg from age 7 onwards. Memory Breg increased progressively from age 3 onwards. In conclusion, the number of Treg frequencies spans a wide range depending on the immunophenotypic definition used despite a good level of correlation exists between them. The decline in numbers and maturation process with age occurs earlier in Breg than in Treg.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1283981/fullTreg cellBreg cellFoxP3immunophenotypingIPEXchild
spellingShingle Yiyi Luo
Yiyi Luo
Yiyi Luo
Daniel Acevedo
Daniel Acevedo
Daniel Acevedo
Alexandru Vlagea
Alexandru Vlagea
Anna Codina
Ana García-García
Ana García-García
Ana García-García
Angela Deyà-Martínez
Angela Deyà-Martínez
Angela Deyà-Martínez
Celia Martí-Castellote
Celia Martí-Castellote
Celia Martí-Castellote
Ana Esteve-Solé
Ana Esteve-Solé
Ana Esteve-Solé
Laia Alsina
Laia Alsina
Laia Alsina
Laia Alsina
Changes in Treg and Breg cells in a healthy pediatric population
Frontiers in Immunology
Treg cell
Breg cell
FoxP3
immunophenotyping
IPEX
child
title Changes in Treg and Breg cells in a healthy pediatric population
title_full Changes in Treg and Breg cells in a healthy pediatric population
title_fullStr Changes in Treg and Breg cells in a healthy pediatric population
title_full_unstemmed Changes in Treg and Breg cells in a healthy pediatric population
title_short Changes in Treg and Breg cells in a healthy pediatric population
title_sort changes in treg and breg cells in a healthy pediatric population
topic Treg cell
Breg cell
FoxP3
immunophenotyping
IPEX
child
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1283981/full
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