title: Absence of cross-presenting cells in the salivary gland and viral immune evasion confine cytomegalovirus immune control to effector CD4 T cells.
abstract: Horizontal transmission of cytomegaloviruses (CMV) occurs via prolonged excretion from mucosal surfaces. We used murine CMV (MCMV) infection to investigate the mechanisms of immune control in secretory organs. CD4 T cells were crucial to cease MCMV replication in the salivary gland (SG) via direct secretion of IFNγ that initiated antiviral signaling on non-hematopoietic cells. In contrast, CD4 T cell helper functions for CD8 T cells or B cells were dispensable. Despite SG-resident MCMV-specific CD8 T cells being able to produce IFNγ, the absence of MHC class I molecules on infected acinar glandular epithelial cells due to viral immune evasion, and the paucity of cross-presenting antigen presenting cells (APCs) prevented their local activation. Thus, local activation of MCMV-specific T cells is confined to the CD4 subset due to exclusive presentation of MCMV-derived antigens by MHC class II molecules on bystander APCs, resulting in IFNγ secretion interfering with viral replication in cells of non-hematopoietic origin.
authors: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors: Senta M
authors: SM
authors: Walton
authors: Sanja
authors: S
authors: Mandaric
authors: Nicole
authors: N
authors: Torti
authors: Albert
authors: A
authors: Zimmermann
authors: Hartmut
authors: H
authors: Hengel
authors: Annette
authors: A
authors: Oxenius
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D045142:Cross-Priming; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D057131:Immune Evasion; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D012469:Salivary Glands / Q000821:virology*; D014779:Virus Replication
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma