Protein that may stimulate production of T-cells identified

Washington, July 23 : A protein called Wnt4, which can stimulate the production of T-cells, the white blood cells that recognise and kill infectious agents, has been identified by Canadian and Finnish researchers

With Wnt4, it will now be possible to combat age-related decline in immune response, thanks to the work of Dr. Claude Perreault and his team of researchers at the Institute for Research in Immunology and Cancer (IRIC) at the Universite de Montreal in Canada and the University of Oulu in Finland.

One of the most obvious signs of the age-related decline of the immune system is the atrophy of the thymus, a small gland at the base of the neck where T cells mature. This decline becomes significant towards the age of 50.

It is caused not only by a decreased output of T cells from the thymus, but also by a decreased ability to recognize new antigens. The result is an increased susceptibility to infection as well as a lowered resistance to the immunosuppressive effects of chemotherapy.

"Thymic atrophy is a major public health problem. It compromises the efficacy of vaccination and weakens the resistance to common viruses, for instance to the respiratory syncytial virus (RSV), which is responsible each year for the hospitalization of more than 150,000 people in the U.S.

This is due to the fact that 'old' T cells are not equipped to face the threat of new foreign bodies, whether they are viruses or tumours," said Dr. Perreault.

The researchers induced overproduction of the Wnt4 protein in the cells of the mouse immune system and saw the stimulatory effect this protein exerts on the development of white blood cells.

By using molecular markers that are specific to the different stages of cell maturation, the researchers determined that elevated levels of Wnt4 led to a marked increase in the number of white blood cell progenitors, and of immature T cells in the thymus in particular.

On the other hand, they found that deletion of the Wnt4 gene and lack of the corresponding protein was linked with a decrease in the number of T cell progenitors in the thymus.

After showing that Wnt4 could stimulate thymopoiesis, the name given to the production of T cells in the thymus, researchers wanted to understand the mode of action of the protein.

Isabelle Louis, a graduate student, and Dr. Krista Heinonen, a postdoctoral fellow, analyzed the changes in gene activity triggered by exposure to Wnt4 and found that the results were conclusive: Wnt4 increases the number of T cell progenitors by inducing the expression of genes involved in cell survival.

IRIC researchers also showed that Wnt4 does not mediate these changes in gene expression through the intracellular pathway normally activated by members of the Wnt family, i.e. stabilization of a signalling protein called -catenin, but rather through an alternative pathway involving members of the JNK family of proteins.

Now the researchers are investigating ways to capitalize on its discovery to develop new therapeutic agents.

The study is published in the latest edition of the journal Immunity.

ANI