T cells surround a blood vessel in the thymus.
T cells (blue) surround a blood vessel (green) in the thymus

Your body’s immune system is continually fighting off attacks to protect you from disease and infection. New research from the University of Birmingham is uncovering how T cells, key defenders in this process, leave the thymus and enter the peripheral circulatory system.

The study led by Professor Graham Anderson and Dr William Jenkinson is published in the Journal of Experimental Medicine. Based in the Institute of Immunology and Immunotherapy, the research team focus their efforts on investigating how the thymus operates to control T cell development.

T-cells defend the body against both bacterial and viral challengers, as well as tumour formation. Development of T cells takes place in an organ called the thymus, where an educational programme ensures that T cells learn friend from foe, thereby helping to prevent the formation of T cells that can otherwise cause autoimmune disease.

Despite the importance of T cells for the development and maintenance of effective immune protection, the mechanisms that control the timing and rate of T cell output from the thymus remain surprisingly poorly understood.

The study reveals that endothelial cells, that form the walls of blood vessels, act as gate-keepers for thymus T cell emigration. For the first time, it is revealed that expression of the molecule Lymphotoxin b receptor by endothelial cells controls export of T cells from the thymus.

In a further finding, the new research reveals that only the most mature T cells undergoing development in the thymus are provided with a licence to emigrate.

Dr Jenkinson, from the Institute of Immunology and Immunotherapy, commented: “Ensuring that only the most mature T cells leave the thymus may be important to ensure that T cells spend a sufficient period of time in the thymus. This may help to prevent the export of uneducated T cells that could otherwise target the body’s own tissues and drive autoimmune disease.”

This study builds on work from the same research team led by Professor Anderson, which has previously revealed that the Lymphotoxin b receptor also controls T cell precursor entry into the thymus. Importantly, stimulation of the Lymphotoxin b receptor pathway was also found to enhance T cell production in models of bone marrow transplantation.

Collectively these studies may ultimately help efforts to improve immunity in settings where reduced T cell immunity can make individuals susceptible to infections. For example, in the elderly or patients undergoing therapies for eradication of blood cancers.

Dr Jenkinson, added: “If we can try to understand the fundamental mechanisms that control production and emigration of T cells from the thymus, we may be able to identify novel targets that could ultimately aid development of therapeutic strategies aimed at enhancing T cell production and immunity”.

This work was supported by funding provided by the Biotechnology and Biosciences Scientific Research Council (BBSRC) and Medical Research Council (MRC).