By Edyta Zielinska
Auto-ups and -downs
S. Tsai et al., “Reversal of autoimmunity by boosting memory-like autoregulatory T cells,” Immunity, 32:568-80, 2010.
Autoimmune diseases such as multiple sclerosis develop over many years and result in chronic diseases that flare and subside. While trying to kill the cells responsible for the disease in mice, Pere Santamaria at the University of Calgary and colleagues activated a set of mysterious immune cells—and in the process, potentially offered both a new explanation for why inflammation comes and goes, and a new way to reverse the disease.
The plan was to create nanoparticles that would only kill the T cells attacking healthy tissue in mice, leaving the normal immune system intact. “But it didn’t work,” says Santamaria—at least, not how he expected.
Rather than killing immune cells, Santamaria found that his nanoparticles activated a population of autoreactive CD8 T cells that were present in diseased tissue, but whose function was unknown. They showed that the cells, when activated by the nanoparticles, suppressed the activation of more aggressive T cells that attack healthy tissue, thereby reducing autoimmune inflammation. The cells’ function defined, the authors reasoned that these autoreactive cells may become activated after each flare-up of autoimmunity, causing inflammation to wax and wane.