Clinical Information

Naive T cells are generated in the thymus and exported to peripheral blood to form the peripheral T-cell repertoire. There is a decrease in naive T cells derived from the thymus with age due to age-related decline in thymic output. Recent thymic emigrants (RTE) typically refers to those populations of naive T cells that have not diluted their TREC (T-cell receptor excision circles) copies by homeostatic or antigen-driven cell division. Naive T cells can be long-lived in the periphery and postpuberty, and in adults, peripheral T-cell homeostasis is maintained by a balance of thymic output and peripheral T-cell expansion, this proportion changes with age. In infants and prepubertal children, the T-cell repertoire is largely maintained by thymic-derived naive T cells. RTE express TREC indicative of naive T cells derived from the thymus.(1) In the CD4 T-cell compartment, it has been shown that naive CD45RA+ T cells coexpressing CD31 had a higher frequency of TREC compared to T cells lacking CD31.(2) The higher proportion of TREC+ naive T cells indicate a more recent thymic ontogeny since TREC can be diluted by cell division (since they are extrachromosomal).

It has been shown that CD31+CD4+ T cells continue to possess a relatively higher proportion of TREC despite an age-related 10-fold reduction after the neonatal period.(3) CD4 RTE (CD31+CD4+CD45RA+) have longer telomeres and higher telomerase activity, which, along with the increased frequency of TREC positivity, suggests a population of T cells with low replicative history.(3) The same study has also shown that CD31+ CD4+ T cells are an appropriate cell population to evaluate thymic reconstitution in lymphopenic children post-hematopoietic cell transplant.(3) A Mayo study (unpublished) shows that the CD31 marker correlates with TREC-enriched T cells across the spectrum of age and correlates with thymic recovery in adults after autologous hematopoietic cell transplantation.(4) CD31+ CD4 RTE have also been used to evaluate T-cell homeostatic anomalies in patients with relapsing-remitting multiple sclerosis.(5)

For patients with DiGeorge syndrome (DGS)-a cellular immunodeficiency associated with other congenital problems including cardiac defects, facial dysmorphism, hypoparathyroidism, and secondary hypocalcemia, and chromosome 22q11.2 deletion (in a significant proportion of patients)-measurement of thymic function provides valuable information on the functional phenotype, ie, complete DGS (associated with thymic aplasia in a minority of patients) or partial DGS (generally well-preserved thymic function seen the in the majority of patients). Thymus transplants have been performed in patients with complete DGS but are typically not required in partial DGS. There can be change in peripheral T-cell counts in DGS patients with age.(6)