private correspondence

Medullary thymic epithelial cells (mTECs) con-tribute to self-tolerance through the ectopic ex-pression of tissue-specific antigens (TSAs) in the thymus (Derbinski et al., 2001; Anderson et al., 2002; Metzger and Anderson, 2011). This TSA expression in mTECs is largely dependent on autoimmune regulator (Aire), which is expressed in mature mTECs (Gäbler et al., 2007; Gray et al., 2007; Metzger and Anderson, 2011). Through the recognition of TSAs, developing autoreactive T cells are either negatively selected from the pool of developing thymocytes or recruited into the regulatory T (T reg) cell lineage (Liston et al., 2003; Anderson et al., 2005; DeVoss et al., 2006; Shum et al., 2009; Taniguchi et al., 2012; Malchow et al., 2013). The overall importance of this process is underscored by the development of a multi-organ autoimmune syndrome in patients or mice with defective AIRE expression (Consortium, 1997; Nagamine et al., 1997; Anderson et al., 2002). Although central tolerance provides pro-tection against autoimmunity, this process also represents a challenge for anti-tumor immunity (Kyewski and Klein, 2006; Malchow et al., 2013). Because many of the TSAs expressed in the thy-mus are also expressed in tumors, high-affinity effector T cells capable of recognizing tumor self-antigens may normally be deleted in the thy-mus (Bos et al., 2005; Cloosen et al., 2007; Träger et al., 2012; Zhu et al., 2013). Transiently sup-pressing central tolerance by depleting mTECs or modulating Aire expression may provide