Suppression of Th1 and Th17, but not Th2, responses in a CD8+ T cell-mediated model of oral tolerance

Abstract

The role of CD8+ T cells in oral tolerance remains unclear. To address this, we developed a model to induce CD8+ Tregs by feeding the major histocompatibility complex class I immunodominant epitope of OVA, OVA(257-264). OVA(257-264) feeding induced tolerance similar to that observed in OVA protein-fed mice, capable of suppressing the production of Th1 and Th17 cytokines and inhibiting a Th1-driven delayed-type hypersensitivity response following immunization with whole OVA (wOVA) protein. OVA(257-264) peptide-induced suppression could be transferred to naive mice with CD8+ cells, but not CD8-depleted cells, isolated from mesenteric lymph nodes of peptide-fed mice. Interestingly, while capable of inhibiting Th1 and Th17 responses, OVA(257-264) feeding could not suppress any feature of a Th2 inflammatory response, though OVA protein feeding could, suggesting that these cells function through a different mechanism than their CD4+ counterparts generated in response to feeding with wOVA. Thus, CD8+ T cells are functionally capable of mediating tolerance to Th1 and Th17 responses.