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Genetic evidence points to potential therapeutic bypass for autoimmune process
Date:3/2/2009

cause it shows the flexibility of the immune system to regulate T cell responses. If we understand the molecular requirements of these pathways we can potentially use these as targets for therapeutic intervention which is the eventual goal."

This may include repressing immune response in autoimmune disease by increasing Treg development, or doing the opposite in chronic infectious diseases by inhibiting Treg development and promoting activation of T cells, said Dr. Hoebe, who started this study with the first author, Michael J. Barnes, a graduate student at The Scripps Research Institute in La Jolla, Calif. The department of Genetics and Immunology at Scripps was the key collaborator on the study.

Dr. Hoebe's lab uses a unique experimental approach, where they randomly introduce genetic mutations in mice that reflect genetic changes in humans. This is done to discover essential genes required for a normal immune system, in this case that of Treg development. With this approach, the researchers identified a mouse that almost completely lacked Treg cells. The researchers determined the cause of this Treg deficiency to be caused by a specific point mutation in the Carma1 gene, which they named the king mutation.

The researchers took the Carma1-deficient mice and infected them with a mouse variant of human cytomegalovirus which is related to herpes and chickenpox viruses and can remain dormant or cause serious illness in people with compromised immune systems. Although the mice lacked thymus-derived Treg cells, they still had small pools of peripheral Treg cells that greatly expanded after the animals were infected with the virus.

To further investigate the requirements for Treg development in these mice, the researchers were able to induce Treg cells in external laboratory cell cultures from Carma1-deficient, peripheral T lymphocyte white blood cells. They determined these cells could still be transformed into Treg cells by incu
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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