Quantification of T cell receptor rearrangement excision circles to estimate thymic function: an important new tool for endocrine-immune physiology

Abstract

Although the thymus constitutes a target organ for most protein and steroid hormones, it has been quite difficult to determine the precise control exerted in vivo by the endocrine system upon thymic function. The biological role of the thymus is to ensure the generation of a diversified population of peripheral T cells able to respond to non-self-antigens but nevertheless tolerant to selfantigens. For a long time, thymic function could not be monitored, as a consequence of the absence of adequate technology to differentiate recent thymic emigrants from naive T cells. The generation of T cell receptor (TCR) diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCR and chains. During these processes, by-products of the rearrangements are generated in the form of TCR excision circles (TRECs). As these molecules are lost upon further cell division, their quantification is actually considered as a very valuable tool to estimate thymic function. The most appropriate TREC is Rec-J TREC or signal joint TREC resulting from Rec-J rearrangement (TCRD deletion) that occurs late during thymopoiesis, before V -J rearrangement. Here we describe how TREC quantification is a powerful and reliable method to evaluate the impact of hormones and endocrine disorders upon thymic function.

Expression of Werner and Bloom syndrome genes is differentially regulated by in vitro HIV-1 infection of peripheral blood mononuclear cells

“…These findings support the view that the levels of WRN, BLM and RecQL1 helicases are crucial to guarantee genomic stability in actively proliferating and/or transformed cells [11]. Multiple experimental evidences suggested analogies of T cell dynamics between advanced ageing and HIV infection [19][20][21][22][23][24][25][26][27][28][29][30]. Recently, it has been suggested that through a process of continuous immune activation HIV-1 infection leads to an acceleration in the ageing process of the adaptive immune system, thus contributing to immunodeficiency [31].…”

“…Moreover, a decreasing number of recent thymic emigrants, identified as T cell receptor excision circles (TRECs) [27][28][29], have been observed with ageing and in HIVinfected individuals, while highly active antiretroviral therapy (HAART) treatment leads to an increased thymic output [29,30]. Therefore, there is a developing hypothesis that HIV-1 infection leads to an acceleration of the adaptive immune system ageing process, resulting in a premature exhaustion of immune resources and leading eventually to the onset of immunodeficiency [31].…”

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

“…The human thymus has its highest activity phase in an age group from 0-10 y and shows a major activity drop in the population older than 39 y. Nevertheless, the thymus remains still active in the elderly population (12,13).…”

Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection

“…As previously described, 13,21,22 parallel quantification of each TREC together with the CD3␥ chain (used as a housekeeping gene) was performed for each sample using the LightCycler technology (Roche Diagnostics, Mannheim, Germany). PBMCs were lysed in Tris (10 mM, pH 8.2) Tween-20 (0.05%), NP-40 (0.05%), and Proteinase K (100 g/mL) for 30 minutes at 56°C and then 15 minutes at 98°C.…”