Sara Ferrando-Martínez1, Raquel Lorente2, Dolores Gurbindo3, Ma Isabel De José4, Manuel Leal5, Ma Angeles Muñoz-Fernández6, Rafael Correa-Rocha7. 1. Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain; Laboratorio de Inmunovirología, Instituto de Biomedicina de Sevilla (IBIS), Unidad clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain. 2. Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain. 3. Sección de Inmunopediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 4. Servicio de Enfermedades Infecciosas Infantil, Hospital Universitario "La Paz", Madrid, Spain. 5. Laboratorio de Inmunovirología, Instituto de Biomedicina de Sevilla (IBIS), Unidad clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain. 6. Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. 7. Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain. Electronic address: rafael.correa@iisgm.com.
Abstract
OBJECTIVE: To perform an extensive analysis of the immune status of asymptomatic children with the 22q11.2 deletion syndrome, with special emphasis on the regulatory T cells (Treg) population. STUDY DESIGN: Analysis of thymic function, frequency and absolute counts of immune subsets, and phenotype of Treg were performed in 10 asymptomatic children bearing the 22q11.2 deletion and compared with 12 age-matched, healthy children. RESULTS: Children with 22q11.2 deletion syndrome showed a curtailed thymic output, lower T-cell levels, and a homeostatic deregulation in the CD4 T-cell compartment, characterized by a greater proliferative history in the naïve CD4 T-cell subset. Treg numbers were markedly reduced in children with 22q11.2 deletion syndrome, and remaining Treg showed mostly an activated phenotype. CONCLUSIONS: Reduced thymic output in children with 22q11.2 deletion syndrome could be related with an increased proliferation in the naïve CD4 T-cell compartment and the consequent Treg activation to ensure that T-cell expansion remains under control. Deregulated peripheral homeostasis and loss of suppressive capacity by Treg could compromise the integrity of T-cell immunity during adulthood and play a relevant role in the increased incidence of autoimmune diseases reported in patients with the 22q11.2 deletion syndrome.
OBJECTIVE: To perform an extensive analysis of the immune status of asymptomatic children with the 22q11.2 deletion syndrome, with special emphasis on the regulatory T cells (Treg) population. STUDY DESIGN: Analysis of thymic function, frequency and absolute counts of immune subsets, and phenotype of Treg were performed in 10 asymptomatic children bearing the 22q11.2 deletion and compared with 12 age-matched, healthy children. RESULTS:Children with 22q11.2 deletion syndrome showed a curtailed thymic output, lower T-cell levels, and a homeostatic deregulation in the CD4 T-cell compartment, characterized by a greater proliferative history in the naïve CD4 T-cell subset. Treg numbers were markedly reduced in children with 22q11.2 deletion syndrome, and remaining Treg showed mostly an activated phenotype. CONCLUSIONS: Reduced thymic output in children with 22q11.2 deletion syndrome could be related with an increased proliferation in the naïve CD4 T-cell compartment and the consequent Treg activation to ensure that T-cell expansion remains under control. Deregulated peripheral homeostasis and loss of suppressive capacity by Treg could compromise the integrity of T-cell immunity during adulthood and play a relevant role in the increased incidence of autoimmune diseases reported in patients with the 22q11.2 deletion syndrome.
Authors: Peilin Zheng; Lenora M Noroski; Imelda C Hanson; Yuhui Chen; Michelle E Lee; Yu Huang; Michael X Zhu; Pinaki P Banerjee; George Makedonas; Jordan S Orange; William T Shearer; Dongfang Liu Journal: J Allergy Clin Immunol Date: 2015-03-03 Impact factor: 10.793
Authors: Michel Lecendreux; Guillaume Churlaud; Fabien Pitoiset; Armelle Regnault; Tu Anh Tran; Roland Liblau; David Klatzmann; Michelle Rosenzwajg Journal: PLoS One Date: 2017-01-20 Impact factor: 3.240
Authors: Adam Klocperk; Zuzana Paračková; Markéta Bloomfield; Michal Rataj; Jan Pokorný; Susanne Unger; Klaus Warnatz; Anna Šedivá Journal: Front Immunol Date: 2018-07-23 Impact factor: 7.561