When the immune system's killing power starts attacking the body's own cells, devastating autoimmune diseases like arthritis can be the result. To prevent this, some immune cells go through a special boot camp in the thymus where they learn how to put the muzzle on overzealous immune cells, scientists report in this month's Nature Immunology. Experts hope that some day these cells may help to treat or even prevent autoimmunity.
T cells kill virus-infected cells and orchestrate our immune responses. Like any soldier, they have to tell friend from foe. Those that can't are weeded out in the thymus. A key test is the interaction between the T cell receptor and the body's own (or "self") peptides, presented on the surface of other cells. A T cell that only binds weakly to self peptides is allowed to exit the thymus and patrol the body, but a T cell that clamps on tightly to self peptides is forced to self-destruct. At least, so the dogma went.
To better understand this process, immunologist Andrew Caton and his colleagues at the Wistar Institute in Philadelphia created two strains of transgenic mice. One had T cells with a high affinity for a certain self peptide; the T cells of the second strain had a 100-fold lower affinity. "We expected that the high-affinity T cells would be deleted in the thymus and the low-affinity ones would be allowed to escape," Caton says. The opposite was true: Instead of being killed in the thymus, the autoreactive T cells abounded in Caton's transgenic mice.
Upon closer inspection, the potentially dangerous escapees turned out to be beneficial. During their days in the thymus, they had developed into a new class of T cells, so-called regulatory or suppressor T cells, which are known to turn off other T cells that are stimulated by the very same peptide. These regulators scour the body looking for autoreactive T cells that may have escaped from the thymus.
The results are "pretty amazing," says immunologist Michael Bevan of the University of Washington, Seattle, because a high-affinity interaction usually means the T cell gets killed. "This might be a new way of keeping autoreactive T cells in check," Bevan says. And perhaps the mechanism is crucial to safeguard against autoimmune diseases, says Caton. "If we understand how regulatory T cells are made," he speculates, "maybe this will allow us to boost or expand these cells" to treat autoimmune diseases.