Direct Evidence for Thymic Function in Adult Humans

Abstract

The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-β V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4+CD45RA+ CD62L+ subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4+CD45RO−CD62L+ and CD4+CD45RO+CD62L+ phenotypes. RTEs were observed to have more than one Vβ rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation.

Thymopoiesis in elderly human is associated with systemic inflammatory status

“…The difficulty in obtaining thymic tissue samples forced us to limit to a cohort with a median age of 68.6 years, which reflects the age of patients who underwent cardiac surgery at our hospital. Human thymus studies usually use an indirect measure, such as the TREC quantification in peripheral blood as a thymic function-related marker (Jamieson et al 1999;Poulin et al 1999), but in this study, we have analyzed the percentage of DP thymocytes as the thymic function direct marker. In addition, we have directly quantified the TREC levels in thymic tissue DNA, where no proliferation induced by activation occurs.…”

“…Nevertheless, none of these works assessed a direct association between thymic function-related markers and peripheral naive subsets. Furthermore, it has been reported (Jamieson et al 1999;Poulin et al 1999) that new T lymphocytes continue to emigrate from the thymus even in adulthood, yet, as far as we know, whether this output is large enough to modify the peripheral naive T-cell pool through an effective lymphopoiesis remains unclear.…”

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

“…Furthermore, the presence of TRECs in the blood of adults suggests residual thymic function beyond adolescence. 26 Numerous dynamic processes also influence TREC measurements. For example, the TREC content of naive T cells is influenced by thymic activity on the one hand, proliferation of cells within that subset and differentiation of TREC-containing cells into a more mature phenotype on the other.…”

Alternatively spliced transcripts of the thymus-specific protease PRSS16 are differentially expressed in human thymus

“…One plausible explanation is that, in those patients, the program of the thymus is set up to a higher output of T cells, similar to the newborn thymus. Even if there is a continuous thymic output of T cells throughout the human lifespan, 28 the morphological changes of the thymus before and during adulthood cause an age-dependent decline in recent thymic emigrants. 29 This may reflect that the different thymic stages fit the different requirements, where newborns need to establish very fast an adaptive immune response against a broad repertoire of unknown pathogens.…”