Low thymic output in the 22q11.2 deletion syndrome measured by CCR9⁺CD45RA⁺ T cell counts and T cell receptor rearrangement excision circles

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.