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Salivary gland immunization via Wharton's duct activates differential T‐cell responses within the salivary gland immune system
Author(s) -
Liu Guangliang,
Zhang Fangfang,
Wang Ruixue,
London Steven D.,
London Lucille
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801993r
Subject(s) - salivary gland , gata3 , biology , rar related orphan receptor gamma , immune system , foxp3 , submandibular gland , sublingual gland , foxa2 , immunology , ductal cells , microbiology and biotechnology , transcription factor , endocrinology , immunohistochemistry , biochemistry , gene
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 (T h )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 T h 1 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 T h 2 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 T h 17 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 T h 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