Fig. 2
From: Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
TCR signaling strength decides self-reactive CD4sp T clone fates. Interaction between MHC-II/self peptide complex on mTEC and self-reactive TCR on CD4sp thymocyte produces three types of signaling strength: (1) a strong signal leads to negative selection, resulting in thymocyte depletion; (2) an intermediate signal leads to tTreg generation; (3) a weak signal results in thymocyte differentiation into T conventional (Tcon) cells. We hypothesize that age-related thymic involution shifts signaling strength from strong to intermediate and relatively enhances polyclonal tTreg generation (black arrow—a) ; while in some cases, antigen-specific interactions exhibit an even weaker signal, resulting in diminished antigen-specific tTreg cells and increased antigen-specific Tcon cells (black arrow—b)