A coordinated cellular network regulates tolerance to food

To absorb nutrients and support commensal microbes, the host induces tolerogenic immune responses via peripheral regulatory T cells (pTregs) . Prior studies identified type 1 dendritic cells (cDC1) as initiators of dietary pTregs. However, we now report that food-specific pTreg cells are exclusively induced by the recently identified ROR?t APCs and not by cDCs. Instead, our data suggest that pTreg–cDC1 interactions in steady-state limit the expansion of food-specific CD8aß T cells. This regulation breaks during infection or food poisoning, enabling dietary CD8aß T cells to expand and acquire effector functions in response to mimicked food antigens. Unlike in typical infections, after the pathogen is cleared, dietary CD8aß T cells do not expand in response to their corresponding dietary antigens. Thus, we propose that in response to dietary antigens, tolerance is mediated by a circuit of dedicated antigen-presenting cells (APCs) and T cells. When the host is challenged by infection, this circuit permits the transient expansion of protective effector responses without compromising the overall strategy of tolerance that ensures safe food consumption. Overall design: C57BL66 week old female mice were either fed OVA or just PBS by gavage and later infected with Listeria expressing OVA (LmOVA). Small intestine lamina propria was extracted and used for analysis.