Insight into normal thymic activity by assessment of peripheral blood samples

Abstract

The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.

DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire

“…We further used Q-PCR assays and validated that the expression of PRKDC was augmented in peripheral T cells from these 4 patients after decitabine treatment compared with those before epigenetic therapy (Figure 6F). In addition, we detected the TCR excision circles (TRECs), which could indirectly assess the thymus output of newly derived T cells [23]. As shown in Figure 6G, an increase in TRECs levels was observed in UPN1 to UPN4 following decitabine treatment.…”

“…The epigenetic modifying agents were recently reported to induce the expression of Th1-type chemokines and promote effector T cell trafficking to the tumor environment [34]. Thus, decitabine-based therapy would enhance anti-tumor immunity [23]. …”

Quantification of specific T and B cells immunological markers in children with chronic and transient ITP

“…The breakage in the DNA strand forms on the one hand functional receptors (coding joint recombination sites) and on the other hand, creates by‐products (signal joint recombination sites) called TCR excision circles (TRECs) and kappa‐deleting recombination excision circles (KRECs), respectively. TREC and KREC are circular episomic DNA, therefore they do not divide in the cell and do not appear in the daughter cells . Measuring the amount of copies of TREC in peripheral blood T cells is a marker of thymic function and the creation of new T cells .…”

“…Clinically, these indices were found to be very effective in evaluating immune deficiencies of T and B cells . In addition, they have been very useful in assessing the activity of autoimmune diseases …”

“…TREC and KREC are circular episomic DNA, therefore they do not divide in the cell and do not appear in the daughter cells. 18,19 Measuring the amount of copies of TREC in peripheral blood T cells is a marker of thymic function and the creation of new T cells. [18][19][20] KREC is a marker of new B cells that originated from the bone marrow.…”