title: Low thymic output and reduced heterogeneity of alpha/beta, but not gamma/delta, T lymphocytes in infants with ataxia-telangiectasia.
abstract: Ataxia-telangiectasia, a genetic disease caused by the homozygous mutation of the ATM gene, is frequently associated to a deficit of humoral and cellular immune functions. A decreased thymic output and skewed T cell and B cell receptor repertoires have been recently described in children over 7 years of age and in adults with this disease and have been proposed as a possible explanation for the immunodeficiency. To understand whether T cell defects arise early in life as a consequence of ATM gene mutations, we analysed the extent of thymic function by measuring the number of naïve T cells and by studying the heterogeneity of T cells by means of heteroduplex analysis, in two children less than 2 years old with a remarkable reduction of T cell count. We found that the thymic output is decreased in babies with ataxia-telangiectasia if compared with that observed in age-matched normal babies. The low production of new T cells is associated to a reduction of the diversity of alpha/beta, but not gamma/delta, T lymphocytes. Our data indicate that ATM mutation limits the generation of a wide alpha/beta T cell repertoire and this feature can be responsible for the immunodeficiency observed in ataxia-telangiectasia babies.
authors.affiliation: Pediatric Neuropsychiatry, Spedali Civili of Brescia, Brescia, Italy. limberti@yahoo.it
authors.forename: R
authors.initials: R
authors.lastname: Micheli
authors.forename: S
authors.initials: S
authors.lastname: Pirovano
authors.forename: G
authors.initials: G
authors.lastname: Calandra
authors.forename: M
authors.initials: M
authors.lastname: Valotti
authors.forename: A
authors.initials: A
authors.lastname: Plebani
authors.forename: A
authors.initials: A
authors.lastname: Albertini
authors.forename: L
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000293:Adolescent; D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D013950:Thymus Gland / Q000276:immunology* / Q000503:physiopathology*