Balance of the immune system determined by newly discovered T cells

26 July 2011
A newly discovered cell type helps to determine the balance of the immune system. The cells are derived from FoxP3(+) regulatory T cells, which recently have been demonstrated to suppress disease during transplantation. Nature Medicine and Blood, two high-ranking scientific journals, are publishing findings by the team of Adrian Liston from VIB and K.U.Leuven about this discovery.
Innumerable people suffer from immune system disorders. If the immune system is overactive, it can result in allergies and autoimmune diseases such as Systemic lupus erythematosus (SLE). If the immune system is not active enough, infections or tumors occur. It is therefore essential to maintain the right balance.
Adrian Liston from VIB-K.U.Leuven is investigating a new type of cell that helps to maintain this balance. His ‘follicular regulatory T cells’ (Tfrs) suppress the process by which antibodies are produced during infections and SLE. The Tfrs themselves are daughter cells of FoxP3(+) T cells, key regulators of the immune system.
From lupus to cancer
In order to prevent disease the immune system needs to be in balance. If the system is too active, it produces antibodies against harmless substances, as is the case with allergies. An overactive immune system can even attack the body’s own tissues, causing autoimmune diseases such as lupus, rheumatism and diabetes. However, an insufficiently active immune system opens the way for rampant infections and tumors.
A complex network of regulatory cells is active to maintain this balance in our bodies. This must ensure that the immune system is sufficiently active and selective so that pathogenic intruders are recognized and eliminated in good time, but at the same time that it does not get out of control. This network of regulatory and activating cells is a long way from being fully unraveled. Dozens of researchers around the world are working to map this network.
A new switch
Adrian Liston, an Australian researcher who joined VIB and the K.U.Leuven in 2009, is one of the key researchers in this field. With the Tfr cells, he may be on the track of an important player in that network. After all, these cells inhibit the activity of a key class of T helper cells – the so-called ‘T follicular helper cells’ – that support the antibody-producing B-cells via growth and survival signals. In other words, the Tfr cells keep the production of antibodies under tight control.
The recent research results in every way strengthen Adrian Liston’s conviction that the immune suppression capacity of regulatory T cells provides an important starting point for new treatments against autoimmune diseases. As T follicular helper cells are the key driver of autoimmune disease in SLE, the newly discovered Tfr cell represents a new strategy to suppressing this disease.
This Tfr research is a joint collaboration between researchers from VIB-K.U.Leuven, the Australian National University (Aus) and the University of Cambridge (U.K.).
Linterman et al, Foxp3(+) follicular regulatory T cells control the germinal center response, Nat Med, 2011, doi:10.1038/nm.2425
Tian L et al, Foxp3+ regulatory T cells exert asymmetric control over murine helper responses by inducing Th2 cell apoptosis, Blood, 2011, doi:10.1182/blood-2011-04-346056

TFR derive from Foxp3+ precursors