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

Salivary 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, GATA3, and RAR-related orphan receptor γ, thymus-specific isoform (RORγt) (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.