Singapore, Jul 20, 2009: Dr Ming-Zong Lai, a Research Fellow at the Institute of Molecular Biology, Academia Sinica and his colleagues have discovered that a molecule called "Deltex1", which is said to contribute to immune tolerance. Their results, published in the July 17 issue of the highly influential immunology journal Immunity, are expected to contribute to the future development of immunological therapy.

Immune tolerance prevents the adaptive immune system from attacking the body's own tissues. One of the major mechanisms of immune tolerance is the induction of T-cell anergy which prevents T-cell activation. "Anergy" is the term used in immunobiology to describe lack of reaction by the body's defense mechanisms to antigens: so if immune cell anergy is induced, it means that immune cells are not activated and therefore the body’s immunity is compromised.

 

Dr Lai and his group are said to have advanced understanding of these processes by discovering that a molecule called Deltex1 functions to suppress T cell activation. By using transgenic mice, the researchers found that Deltex1 profoundly prevents the activation of T cells. Further study revealed that Deltex1 utilizes at least three distinct mechanisms to prevent T-cell activation: Deltex1 promotes the degradation of a key upstream enzyme (kinase), inactivates another enzyme (kinase), and further targets several biological processes within the cell (signaling cascades).

Using these three inhibitory processes, according to the researchers, the Deltex1 effectively blocks the activation signals in T cells, rendering them inactive. Conversely, if the Deltex1 gene is deleted, T cells become hyper-active. In mice lacking Deltex1, autoantibodies are spontaneously produced, causing inflammation in the lung and liver, indicating that autoimmune diseases are induced in the absence of Deltex1.

 

The findings of the research are expected to help in the future development of immunological therapy for the prevention of graft rejection and the elimination of cancer cells.