Harnessing Dendritic Cells to Control Destructive T Cells

Cytotoxic T cells known as CD8+ T cells are strongly associated with the development of type 1 diabetes. By harnessing the natural role of the dendritic cell, another type of immune cell, JDRF-funded researchers have found a way to keep the destructive CD8+ T cells in check. Under normal circumstances, dendritic cells present self-proteins to T cells in a manner that leads to deletion or inactivity of the T cells, thus protecting the body from autoimmune disease, explained principal investigator Teresa P. DiLorenzo. Relying on this information, the researchers constructed a specialized antibody that delivered a small beta cell protein to the dendritic cells of mice that develop diabetes. After recognizing and responding to this antigen, diabetes-causing T cells that had been introduced into the mice began to divide, but they were later deleted by the immune system—indicating a positive “tolerogenic” response. The immunotherapeutic may have facilitated this process by increasing the amount of beta cell antigen available to the tolerizing dendritic cells. Future antigen-based treatments may need to be broader in scope, however, given that multiple beta cell antigens are likely targeted for autoimmune attack. The study is reported in the journal Proceedings of the National Academy of Sciences.