T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome

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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) Vβ families and missing Vβ 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. (Blood. 2004;103:1020-1025)