Peripheral tolerance prevents autoimmune responses mediated by autoreactive T cells, and conventional dendritic cells (cDCs) can present tissue-specific antigen (TSA) and induce anergy and deletion of autoreactive T cells in local lymph nodes. Here, Joeris et al. examined the role of intestinal cDC1 presenting TSA derived from intestinal epithelial cells (IECs) in driving cross-tolerance of CD8+ T cells. cDC1 mediated peripheral tolerance by converting naïve CD8+ T cells to intestine-homing CCR9+ FoxP3+CD8+ Tregs, which involved programmed death ligand 1 (PD-L1), retinoic acid (RA), and transforming growth factor β (TGFβ) derived from intestinal cDC1. CD103 expression was needed for the tolerogenic function of these FoxP3+CD8+ Tregs. These findings highlight a role for cDC1-mediated induction of FoxP3+CD8+ Tregs in cross-tolerance to TSA in the intestine.
Although CD8+ T cell tolerance to tissue-specific antigen (TSA) is essential for host homeostasis, the mechanisms underlying per