We study how T cell mediated immune tolerance develops in the thymus

T lymphocytes play a central role in the defence of the organism against pathogens (viruses, bacteria, parasites) and tumours. The mechanisms involved in the development of T cells in the thymus necessarily imply the generation of potentially dangerous T cells. To avoid autoimmune pathology, these cells need to be neutralised (by the process of "negative selection") before they leave the thymus. This is the first way the thymus ensures immune-tolerance. The second one involves the generation of so-called "regulatory T cells" which prevent autoimmune pathology and chronic inflammation, protect the foetus from rejection by the mother's immune system, fine-tune immune-responses to pathogens, but unfortunately also inhibit immune responses towards tumours. The group now led by Prof. Joost van Meerwijk studies Treg development in the thymus.

The regulatory T cell repertoire is autospecific
​

In accordance with one of their main functions, we were the first to demonstrate that the repertoire of regulatory T cells is enriched in autospecific cells. This allows these cells to be activated when and where also the very dangerous autospecific T cells that cause autoimmunity are activated

How does the thymus limit development of regulatory T cells?

The number of regulatory T cells developing in the thymus is much lower than the number of precursors with appropriate antigen-specificity. This suggests that the thymus somehow limits differentiation of regulatory T cells. We showed that limiting the number of precursors does not increase the proportion of cells differentiating into the regulatory lineage, which suggests that precursors are involved in shaping the niche

Paradoxically increased development of regulatory T cells in autoimmune-prone mice

Regulatory T cells protect us from autoimmune pathology. Our finding that in autoimmune-prone mice more of these cells develop was therefore very surprising. Data from our lab also showed genetic control of the development of regulatory T cells. One involved locus is closely linked to the major histocompatibility locus (MHC)
​

Regulatory T cells migrate back to the thymus

We demonstrated that regulatory T cells activated during immune-responses migrate back to the thymus and influence induction of immune-tolerance. We are currently working on further consequences of this intriguing phenomenon