Oral tolerance to systemic vaccination remains intact without RORγt expression in regulatory T cells

• DOI: 10.1016/j.isci.2023.108504
• Publication Date: 2023-11-22T13:56:37Z
• Authors: Nicole B. Potchen; Andrew M.F. Johnson; Kevin Hager; Jessica Graham; Phuong Van; Katelyn H. Lyn-Kew; Lakshmi Warrier; Irene Cruz Talavera; Jennifer M. Lund; James G. Kublin
• Keywords: 0301 basic medicine; Cell biology; 03 medical and health sciences; Science; Immunology; Q; Immune response; Article

Many promising vaccine candidates and licensed vaccines lead to variable immune responses within humans. Studies suggest that environmental exposures in the gastrointestinal tract could contribute to a reduction in vaccine efficacy via immune tolerance at this site; this is partly achieved by a high abundance of regulatory T cells (Tregs). It is unclear if Treg subsets regulate systemic vaccine responses following oral antigen pre-exposure. Here, we implemented a conditional knock-out mouse model of RORγt+ Tregs to examine the role of these cells in mediating this process. Following oral exposure to the model antigen ovalbumin (OVA) prior to immunization, we found similar induction of vaccine-induced antibody responses in mice lacking RORγt expression in Tregs compared to sufficient controls. Use of various adjuvants led to distinct findings. Our data suggest that expression of RORγt+ within Tregs is not required to regulate tolerance to systemic vaccination following oral antigen exposure.