title: Regulatory T cells selectively preserve immune privilege of self-antigens during viral central nervous system infection.
abstract: Regulatory T cells (Tregs) are important for the attenuation of immune reactions. During viral CNS infections, however, an indiscriminate maintenance of CNS immune privilege through Treg-mediated negative regulation could prevent autoimmune sequelae but impair the control of viral replication. We analyzed in this study the impact of Tregs on the development of acute viral encephalomyelitis, T cell-mediated antiviral protection, and prevention of CNS autoimmunity following intranasal infection with the gliatropic mouse hepatitis virus strain A59. To assess the contribution of Tregs in vivo, we specifically depleted CD4(+)Foxp3(+) T cells in a diphtheria toxin-dependent manner. We found that depletion of Tregs had no impact on viral distribution and clearance and did not significantly alter virus-specific CD4(+) and CD8(+) T cell responses. However, Treg depletion led to a more severe CNS inflammation associated with neuronal damage. Dissection of the underlying immunopathological mechanisms revealed the elaborate Treg-dependent regulation of self-reactive CD4(+) T cell proliferation within the CNS-draining lymph node and downtuning of CXCR3 expression on T cells. Taken together, these results suggest that Tregs preserve CNS immune privilege through selective control of CNS-specific Th cells while keeping protective antiviral immunity fully operative.
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragán
authors.forename: Sonja
authors.initials: S
authors.lastname: Firner
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Katharina
authors.initials: K
authors.lastname: Lahl
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
mesh_terms: D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002494:Central Nervous System Infections / Q000276:immunology* / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology* / Q000821:virology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D015704:CD4 Antigens; C515188:Cxcr3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D054367:Receptors, CXCR3