News - 07 Nov `18Research update: BH4 controls growth of killer T-cells


Scientists have uncovered a new way to curb autoimmunity — including vitiligo. A molecule recognized as essential for many functions in neurobiology is now identified as a natural "killer T-cell" controller, thereby pawing way to completely new therapies.

It's probably a good time for a recap that begins with some introspection.


Autoimmune diseases result from an overactive or misdirected immune system. There are more than 80 types of autoimmune disease, and these arise because the immune system attacks healthy tissue, mistaking it for a threat.

"Killer" T-cells are our main defence against viruses and tumours. As a major part of the adaptive immune system, T-cells scan the intracellular environment to target and destroy intruders.

In vitiligo, for reasons yet unclear, T-cells attack and destroy healthy melanocytes that produce color, thereby creating white patches on the skin.


A well-known molecule called tetrahydrobiopterin (BH4) was found to have a previously unknown role: it helps to control the growth of "killer" T cells in the immune system.

What is particularly interesting, is that the discovery concerns the control of T cell growth — as opposed to the cells' activation — when T-cells go nuts for unknown reasons and rage onto healthy cells.

It seems that T cells need BH4 to help them regulate iron and produce energy. By dialing down the amount of BH4, researchers can block T-cell proliferation in autoimmune diseases. The researchers tested some BH4 blockers on mouse models of allergies and autoimmune diseases. The experimental drugs "calmed" auto-aggressive T-cells and stopped inflammation.

The beauty of the new approach is that instead of targeting a single cytokine or class of T cells, researchers can halt proliferation in all disease-related T cells.


The finding should lead to a wide variety of medical uses, ranging from controlling autoimmune diseases, asthma, or allergies to having a new way to trigger anticancer immunity. It may take a while — but hey — we're getting there!


The leaders of the study are researchers at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna and others at the Boston Children's Hospital in Massachusetts. The journal Nature published the findings today, on November 7, 2018.