In the late 1980s and early 1990s many groups showed that thymocytes are subject to a positive and negative selection during their intrathymus differentiation and maturation process. Among these groups, von Boehmer and colleagues (Teh et al., Nature 335:229-235, 1988) using TCR transgenic mice demonstrated that thymocytes undergo positive selection in the cortex of the thymus by binding of the TCR with the MHC expressed by the cortical epithelial cells. Also, Marrack and Kappler and their colleagues showed that once thymocytes migrate into the thymus medulla, they undergo a negative selection process leading to apoptosis and tolerance to specific antigens (Kappler et al., Cell 49:273-280, 1987; Kappler et al., Nature 332:35-40, 1988).
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