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Suppressing unwanted immune responses without compromising host immunity against pathogens is considered the holy grail of immunology. Lack of responsiveness to self-antigens is normally maintained by multiple mechanisms, including the suppressive activities of several T cell subsets. In this issue of the JCI, Jiang and colleagues define a CD8(+) suppressor T cell subset in humans that recapitulates a regulatory pathway previously described in mice. These investigators further show that patients with type 1 diabetes have defects in their CD8(+) suppressor T cells, thus identifying these cells as potential therapeutic targets in human disease.