News & Research

By: Felicia Breedy

James Gardner, an MD/PhD student at the University of California, San Francisco is the recipient of an ADA Clinical Scholars Award. He has conducted research in the laboratory of Mark Anderson on a project entitled “Identification and characterization of novel Aire-expressing stromal cells within the secondary lymphoid organs.” The study identified a new type of cell that may be important in preventing autoimmune diseases like type 1 diabetes.

T-cells work as part of the immune system and develop in the thymus. There they are taught how to recognize and destroy foreign invaders like bacteria and viruses, while also learning how to avoid attacking “self” tissues like one’s own pancreas. Under normal circumstances any T-cells that attack “self” cells are eliminated. When this fails to happen, autoimmune diseases such as type 1 diabetes can occur.

A unique gene, called the AutoImmune REgulator (Aire), allows a group of specialized educator cells in the thymus to teach developing T-cells how to identify and not attack “self.” Originally it was believed that this T-cell education process occurred only within the thymus. But Gardner, along with his colleagues, has identified a novel population of extrathymic Aire-expressing cells (eTACs), educator cells that exist outside of the thymus and are disseminated throughout the rest of the body. These eTACs reside primarily in the lymph nodes and spleen, sites where the T-cells patrol once they leave the thymus. The research demonstrates that eTACs can directly interact with and delete self-reactive T-cells.

This work suggests that these novel cells may act as a back-up or secondary system and eliminate rogue T-cells that are “self”-reactive but escaped detection and elimination in the thymus. Understanding the mechanisms the body normally uses to prevent autoimmunity can lead to future insight on how to prevent and treat illnesses such as type I diabetes. The results of this work are published in the August 8th issue of Science.

(Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X, Johannes KP, Su MA, Chang HY, Krummel MF, Anderson MS. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 2008 Aug 8;321(5890):843-7)