Abstract
Activated T cells have been shown to be able to recirculate into the thymus from the periphery. The present study was aimed to elucidate the functional consequences of thymic homing of activated T cells upon developing thymocytes and thymic epithelial cells (TEC). In the presence of activated T cells, especially CD4+ T cells, T cell development was found to be inhibited in thymic organ cultures with markedly reduced cellularity. Thymic transplantation demonstrated that the inhibitory effect was most likely due to a defective microenvironment. As the major component of the thymic stroma, the TEC compartment was severely disturbed after prolonged exposure to the activated T cells. In addition to reduced cell proliferation, TEC differentiation was heavily skewed to the mTEC lineage. Furthermore, we demonstrated that RANKL highly expressed by activated CD4+ T cells was primarily responsible for the detrimental effects. Presumably, excessive RANK signaling drove overproduction of mTECs and possibly exhaustion of epithelial progenitors, thereby facilitating the deterioration of the epithelial structures. These findings not only reveal a novel activity of activated T cells re-entering the thymus, but also provide a new perspective for understanding the mechanism underlying thymic involution.
Highlights
The thymus is a primary immune organ responsible for the development of T lymphocytes
T cell development was examined at day 6 and 12, two time points each associated with a wave of thymocyte development normally seen in FTOC41, 42
In addition to a 60% decrease in total thymocytes (Fig. 1a), co-culture with activated CD4+ T cells resulted in a remarkable suppression of double positive (DP) cell production, which was accompanied by proportional increases of CD4 and CD8 single positive (SP) cells (Fig. 1b, upper and c)
Summary
The thymus is a primary immune organ responsible for the development of T lymphocytes. Hematopoietic progenitors seeding the thymus undergo proliferation, differentiation, T cell receptor (TCR) gene rearrangement, positive and negative selections, and functional maturation, culminating in the generation of a T cell repertoire capable of responding to a diverse array of foreign antigens but tolerant to self antigens[1, 2]. During this process, T cell precursors migrate through structurally and functionally distinct cortical and medullary regions. Is the presence of peripheral T cells in the thymus merely an epiphenomenon or are they destined to fulfill some relevant physiological functions ? Despite controversy, evidence is emerging that these cells may participate in the shaping of the T cell repertoire by delivering self antigens into the thymus[35, 36, 38,39,40]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
