Endocrine Abstracts

The T cell immune system exists in a state of balance, poised to react to invading pathogens but at the same time constantly being restrained from attacking our own tissues. Several strategies are employed in order to minimise our own self-reactivity. First amongst these processes is the deletion of T cells in the thymus, however this process is incomplete and self-reactive T cells still populate our immune systems. A second layer of control is exerted by regulatory T cells (Treg) which act to restrain self-reactivity by dominantly suppressing T cell responses. As expected, deficiency in Treg results in profound auto- immune dysregulation polyendocrinopathy and enteropathy X-linked syndrome(IPEX). How Treg function to prevent autoimmunity is therefore of considerable interest. The protein CTLA-4 is highly expressed on Treg and is also associated with a number of autoimmune diseases in genome wide studies. We have recently identified a novel molecular basis for CTLA-4 function where CTLA-4 acts as a molecular ‘hoover’ removing stimulatory ligands from antigen presenting cells (1). This talk will discuss the impact of CTLA-4 on regulatory T cell function along with strategies for enhancing regulatory T cell control of responses relevant to autoimmune disease.

Reference

1. Qureshi OS, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 2011; 332 (6029): 600–3.

Declaration of funding

This work was supported by the BBSRC grant H013598/1.