Dendritic cells stimulate production of immune-repressing T cells (9/15/2007)

Regulatory T cells (also known as T regs) suppress some of the immune system's more inappropriate responses, preventing it from attacking the body's own tissues and stifling its activity once invading microbes have been fought off. But while researchers knew that these cells could be exploited for treating conditions such as allergy, autoimmune disease and transplant rejection, they didn't know how to stimulate their production. Now, new research by Ralph Steinman, Henry G. Kunkel Professor and head of Rockefeller University's Laboratory of Cellular Physiology and Immunology, and first author Sayuri Yamazaki, a research associate in the Steinman lab, shows that dendritic cells are largely responsible for turning naïve, unspecialized T cells into T regs.

Because different T regs suppress different immune responses, Steinman and Yamazaki were interested in understanding how the cells differentiate so that they could elicit production of suppressor cells that respond to specific foreign molecules or antigens. The study, published online by the journal Blood, is the first to compare the role of dendritic cells to other immune cells in T reg differentiation and demonstrates yet another facet of the versatile dendritic cell - a cell already known for its role in guiding immune response and one that holds great potential for revolutionizing HIV vaccines and cancer therapies.

Once the researchers had determined that dendritic cells are responsible for directing the differentiation of naïve T cells into various T regs, they investigated the possibility of using this system to create specialized immune therapies. Working with a model antigen - a chicken egg protein called ovalbumin - Steinman and Yamazaki found that, through the use of dendritic cells that presented the ovalbumin antigen to naïve T cells, they could create T regs that went on to suppress immune resistance to ovalbumin-expressing tumor cells.

"Ovalbumin is just a model system, and it's a very early step in any immune work-up," Steinman says. "But we have to get it into other systems, using more relevant antigens and more relevant models of immune response."

To do this, he says, future experiments will explore using disease-relevant antigens, such as those associated with autoimmunity or allergy, with the ultimate goal of creating targeted therapies that use the body's own cells to turn off an erroneous immune response.

Note: This story has been adapted from a news release issued by Rockefeller University

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