title: Foxp3+ regulatory T cells control persistence of viral CNS infection.
abstract: We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV). Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+) CD25(+) Foxp3(+) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H(22-30) (RIVINREHL) were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p.) application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8(+) effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Dajana
authors.initials: D
authors.lastname: Reuter
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schneider-Schaulies
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000821:virology*; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014709:Vero Cells
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse