title: T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome.
abstract: Patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) typically exhibit thymic hypoplasia, conotruncal cardiac defects, and hypoparathyroidism. The immunodeficiency that results from the thymic hypoplasia has been extensively described and consists primarily of T-cell lymphopenia. A curious feature of the T-cell lymphopenia is that the age-related rate of decline of T-cell numbers is slower in patients than controls. This leads to T-cell numbers in adulthood that are minimally decreased compared with controls. This suggests that homeostatic mechanisms might be acting to preserve the peripheral blood T-cell numbers in patients. We characterized changes in CD4/CD45RA and CD4/CD45RO T-cell populations in patients and controls of various ages and determined T-cell recombination excision circles and telomere length within the CD4/CD45RA population. Patients had evidence of accelerated conversion of naive to memory cells and had evidence of more extensive replicative history within the CD4/CD45RA compartment compared with controls. Oligoclonal T-cell receptor (TCR) Vbeta families and missing Vbeta families were seen more often in patients than controls. These data are consistent with homeostatic proliferation of T cells in patients with limited T-cell production due to thymic hypoplasia.
authors.affiliation: Division of Allergy and Immunology, ARC 1208, CHOP, 34th St and Civic Ctr Blvd, Philadelphia, PA 10104, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Piliero
authors.forename: Amy N
authors.initials: AN
authors.lastname: Sanford
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016615:Telomere / Q000235:genetics; D013950:Thymus Gland / Q000002:abnormalities*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens