The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection

• Published in: Cell reports (Cambridge) Vol. 13; no. 6; pp. 1125 - 1136
• Main Authors: Thom, Jenny Tosca, Weber, Thomas Christian, Walton, Senta Maria, Torti, Nicole, Oxenius, Annette
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.11.2015; Elsevier
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Genes, MHC Class I; Herpesviridae Infections - immunology; Immune Evasion; Mice; Mice, Inbred C57BL; Muromegalovirus - physiology; Salivary Glands - cytology; Salivary Glands - immunology; Virus Replication
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.09.082

Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection. [Display omitted] •MCMV infection leads to effective generation of CD8+ and CD4+ TRM cells in the SG•TRM generation in the SG depends on cognate antigen for CD4+, but not CD8+, T cells•Memory CD8+ T cells protect from localized MCMV challenge infection•Early target cells of intraglandular infection resist MHC I downregulation Tissue-resident memory T (TRM) cells provide efficient protection toward mucosal infection. Thom et al. show that murine cytomegalovirus (MCMV) is a potent inducer of CD8+ and CD4+ TRM cells in the salivary glands, an important site of CMV transmission. These findings offer implications for CMV-based vaccines against mucosa-invading pathogens.