Salivary gland immunization via Wharton's duct activates differential T‐cell responses within the salivary gland immune system

ABSTRACTSalivary glands are a major component of the mucosal immune system that confer adaptive immunity to mucosal pathogens. As previously demonstrated, immunization of the submandibular gland with tissue culture–derived murine cytomegalovirus (tcMCMV) or replication‐deficient adenoviruses expressing individual murine cytomegalovirus (MCMV) genes protected mice against a lethal MCMV challenge. Here, we report that salivary gland inoculation of BALB/cByJ mice with tcMCMV or recombinant adenoviruses differentially activates T helper (Th)1, ‐2, and ‐17 cells in the salivary glands vs. the associated lymph nodes. After inoculation with tcMCMV, lymphocytes from the submandibular gland preferentially express the transcription factor T‐cell–specific T‐box transcription factor (T‐bet), which controls the expression of the hallmark Th1 cytokine, IFN‐γ. Lymphocytes from the periglandular lymph nodes (PGLNs) express both T‐bet and GATA‐binding protein 3 (GATA3), which promotes the secretion of IL‐4, ‐5, and ‐10 from Th2 cells. In contrast, after inoculation with replication‐deficient adenoviruses, lymphocytes from the submandibular gland express T‐bet, GAT A3, and RAR‐related orphan receptor γ, thymus‐specific isoform (ROR/γt) (required for differentiation of Th17 cells) and forkhead box P3 (Foxp3) (required for the differentiation of regulatory T cells). Lymphocytes from the PGLNs were not activated. The differential induction of Th responses in the salivary gland vs. the PGLNs after inoculation with attenuated virus vs. a nominal protein antigen supports the use of the salivary as an alternative mucosal route for administering vaccines.—Liu, G., Zhang, F., Wang, R., London, S. D., London, L. Salivary gland immunization via Wharton's duct activates differential T‐cell responses within the salivary gland immune system. FASEB J. 33, 6011–6022 (2019). www.fasebj.org