Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 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.


METHODS
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.
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.
Sara
S
Ferrando-Martínez
Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.
Raquel
R
Lorente
Sección de Inmunopediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Dolores
D
Gurbindo
Servicio de Enfermedades Infecciosas Infantil, Hospital Universitario "La Paz", Madrid, Spain.
Ma Isabel
MI
De José
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.
Manuel
M
Leal
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.
Ma Angeles
MA
Muñoz-Fernández
Laboratory of Molecular Immunobiology, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain. Electronic address: rafael.correa@iisgm.com.
Rafael
R
Correa-Rocha
D002454:Cell Differentiation; D002675:Child, Preschool; D004062:DiGeorge Syndrome / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007223:Infant; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013950:Thymus Gland / Q000503:physiopathology*