title: The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection.
abstract: 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.
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Jenny Tosca
authors.initials: JT
authors.lastname: Thom
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Thomas Christian
authors.initials: TC
authors.lastname: Weber
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Senta Maria
authors.initials: SM
authors.lastname: Walton
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Torti
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland. Electronic address: oxenius@micro.biol.ethz.ch.
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005805:Genes, MHC Class I; D006566:Herpesviridae Infections / Q000276:immunology*; D057131:Immune Evasion; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000502:physiology; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology*; D014779:Virus Replication