title: Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).
abstract: Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.
authors.affiliation: Laboratory of Cell Biology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pierdominici
authors.forename: F
authors.initials: F
authors.lastname: Mazzetta
authors.forename: E
authors.initials: E
authors.lastname: Caprini
authors.forename: M
authors.initials: M
authors.lastname: Marziali
authors.forename: M C
authors.initials: MC
authors.lastname: Digilio
authors.forename: B
authors.initials: B
authors.lastname: Marino
authors.forename: A
authors.initials: A
authors.lastname: Aiuti
authors.forename: F
authors.initials: F
authors.lastname: Amati
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Novelli
authors.forename: F
authors.initials: F
authors.lastname: Pandolfi
authors.forename: G
authors.initials: G
authors.lastname: Luzi
authors.forename: A
authors.initials: A
authors.lastname: Giovannetti
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D004062:DiGeorge Syndrome / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007135:Immunoglobulin Variable Region; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008213:Lymphocyte Activation; D008297:Male; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D007135:Immunoglobulin Variable Region; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell