title: Direct infection of dendritic cells during chronic viral infection suppresses antiviral T cell proliferation and induces IL-10 expression in CD4 T cells.
abstract: Elevated levels of systemic IL-10 have been associated with several chronic viral infections, including HCV, EBV, HCMV and LCMV. In the chronic LCMV infection model, both elevated IL-10 and enhanced infection of dendritic cells (DCs) are important for viral persistence. This report highlights the relationship between enhanced viral tropism for DCs and the induction of IL-10 in CD4 T cells, which we identify as the most frequent IL-10-expressing cell type in chronic LCMV infection. Here we report that infected CD8αneg DCs express elevated IL-10, induce IL-10 expression in LCMV specific CD4 T cells, and suppress LCMV-specific T cell proliferation. DCs exposed in vivo to persistent LCMV retain the capacity to stimulate CD4 T cell proliferation but induce IL-10 production by both polyclonal and LCMV-specific CD4 T cells. Our study delineates the unique effects of direct infection versus viral exposure on DCs. Collectively these data point to enhanced infection of DCs as a key trigger of the IL-10 induction cascade resulting in maintenance of elevated IL-10 expression in CD4 T cells and inhibition of LCMV-specific CD4 and CD8 T cell proliferation.
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Carmen
authors.initials: C
authors.lastname: Baca Jones
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Christophe
authors.initials: C
authors.lastname: Filippi
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Sowbarnika
authors.initials: S
authors.lastname: Sachithanantham
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rodriguez-Calvo
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ehrhardt
authors.affiliation: Type 1 Diabetes Center, Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation; D002908:Chronic Disease; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D013154:Spleen / Q000473:pathology / Q000821:virology
chemical_list: D016753:Interleukin-10