title: Emergence of distinct multiarmed immunoregulatory antigen-presenting cells during persistent viral infection.
abstract: During persistent viral infection, adaptive immune responses are suppressed by immunoregulatory factors, contributing to viral persistence. Although this suppression is mediated by inhibitory factors, the mechanisms by which virus-specific T cells encounter and integrate immunoregulatory signals during persistent infection are unclear. We show that a distinct population of IL-10-expressing immunoregulatory antigen-presenting cells (APCs) is amplified during chronic versus acute lymphocytic choriomeningitis virus (LCMV) infection and suppresses T cell responses. Although acute LCMV infection induces the expansion of immunoregulatory APCs, they subsequently decline. However, during persistent LCMV infection, immunoregulatory APCs are amplified and parallel the viral replication kinetics. Further characterization demonstrates that immunoregulatory APCs are molecularly and metabolically distinct, and exhibit increased expression of T cell-interacting molecules and negative regulatory factors that suppress T cell responses. Thus, immunoregulatory APCs are amplified during viral persistence and deliver inhibitory signals that suppress antiviral T cell immunity and likely contribute to persistent infection.
authors.affiliation: Department of Microbiology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Wilson
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kidani
authors.forename: Heidi
authors.initials: H
authors.lastname: Elsaesser
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barnard
authors.forename: Laura
authors.initials: L
authors.lastname: Raff
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
authors.forename: Steven
authors.initials: S
authors.lastname: Bensinger
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016753:Interleukin-10