The absence of blatant autoimmunity signs in Carmil2QECd28−/− mice kept under specific pathogen-free conditions suggests that their naive T cells expressing high-affinity self-reactive TCR remain subjected to additional peripheral tolerance mechanisms not relying on PD-1– and transendocytosis-based Treg cell–mediated suppressive mechanisms (Brown and Rudensky, 2023; Gronski et al., 2004; Policheni et al., 2022; Wong et al., 2021). The gene discussed is PDCD1; the disease is Autoimmunity.