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

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

doi:10.1016/j.isci.2023.108504

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

iScience. 2023 Nov 22;26(12):108504. doi: 10.1016/j.isci.2023.108504. eCollection 2023 Dec 15.

Authors

Nicole B Potchen^{1

2}, Andrew M F Johnson¹, Kevin Hager¹, Jessica Graham¹, Phuong Van¹, Katelyn H Lyn-Kew¹, Lakshmi Warrier^{1

2}, Irene Cruz Talavera^{1

2}, Jennifer M Lund^{1

2}, James G Kublin^{1

2}

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
² Department of Global Health, University of Washington, Seattle, WA 98195, USA.

Abstract

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.

Keywords: Cell biology; Immune response; Immunology.

Abstract

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