The thymus and the science of self

The conventional perception asserts that immunology is the science of‘discrimination’between self and non-self. This concept ishowever no longer tenable as effector cells of the adaptive immune system are first conditioned to be tolerant to the body’sownantigens, collectively known as self until now. Only then attain these effectors the responsiveness to non-self. The acquisition ofthis essential state of tolerance to self occurs for T cells in the thymus, the last major organ of our body that revealed its intricatefunction in health and disease. The‘thymus’as an anatomical notion was first notably documented in Ancient Greece althoughour present understanding of the organ’s functions was only deciphered commencing in the 1960s. In the late 1980s, the thymuswas identified as the site where clones of cells reactive to self, termed‘forbidden’thymocytes, are physically depleted as the resultof a process now known as negative selection. The recognition of this mechanism further contributed to the belief that the centralrationale of immunology as a science lies in the distinction between self and non-self. This review will discuss the evidence thatthe thymus serves as a unique lymphoid organ able to instruct T cells to recognize and be tolerant to harmless self before adoptingthe capacity to defend the body against potentially injurious non-self-antigens presented in the context of different challengesfrom infections to exposure to malignant cells. The emerging insight into the thymus’cardinal functions now also provides anopportunity to exploit this knowledge to develop novel strategies that specifically prevent or even treat organ-specific autoim-mune diseases.