Set a thief to catch a thief: self-reactive innate lymphocytes and self tolerance

Self-reactive lymphocytes form part of the peripheral repertoire in healthy individuals. Some of these cells are anergic classical lymphocytes, but a remarkable subset of self-reactive clones is related to innate immunity and many of them bear a partially activated phenotype. In the past few years growing evidence has pointed out the importance of this physiological autoimmunity in self tolerance, with special regard to the role of periportal innate lymphocytes. This population is involved in a wide range of immunoregulatory processes including immune privilege and oral tolerance, providing systemic tolerance to highly tissue-specific antigens as well as microbial epitopes cross-reactive to self. This kind of self-protection is dominantly mediated by self-reactive clones, which commonly play a dual role by acting as potent effectors and regulators at the same time. Here we provide an overview of the field.