title: Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles.
abstract: Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry for direct subtyping of recent thymic emigrant (RTE)-related T cells in 43 patients (aged 1-54 years; median 9 years) from all over Norway and in age-matched healthy controls. Thymic volumes were estimated by ultrasound in patients. TREC levels correlated well with RTE-related T cells defined by co-expression of CD3, CD45RA and CCR9 (r=0.84) as well as with the CD4+ and CD8+ T cell subtypes. RTE-related T cell counts also paralleled age-related TREC reductions. CD45RA+ T cells correlated well with absolute counts of CD4+ (r=0.87) and CD8+ (r=0.75) RTE-related T cells. Apart from CD45RA- T cells, all T cell subsets were lower in patients than in controls. Thymic volumes correlated better with RTE-related cells (r=0.46) than with TREC levels (r=0.38). RTE-related T cells and TREC levels also correlated well (r=0.88) in patients without an identifiable thymus. Production of RTEs is impaired in patients with a 22q11.2 deletion, and CCR9 appears to be a good marker for RTE-related T cells.
authors.affiliation: Section of Endocrinology, Faculty Division Akershus University Hospital, University of Oslo, Oslo, Norway. kari.lima@medisin.uio.no
authors.forename: K
authors.initials: K
authors.lastname: Lima
authors.forename: T G
authors.initials: TG
authors.lastname: Abrahamsen
authors.forename: I
authors.initials: I
authors.lastname: Foelling
authors.forename: S
authors.initials: S
authors.lastname: Natvig
authors.forename: L P
authors.initials: LP
authors.lastname: Ryder
authors.forename: R W
authors.initials: RW
authors.lastname: Olaussen
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000648:ultrastructure*; D004270:DNA, Circular / Q000097:blood*; D004062:DiGeorge Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000032:analysis*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D054388:Receptors, CCR / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C119309:CC chemokine receptor 9; D004270:DNA, Circular; D054388:Receptors, CCR; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human