title: T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner.
abstract: Viral infection of the central nervous system can lead to disability and death. Yet the majority of viral infections with central nervous system involvement resolve with only mild clinical manifestations, if any. This is generally attributed to efficient elimination of the infection from the brain coverings, i.e. the meninges, ependyma and chorioplexus, which are the primary targets of haematogeneous viral spread. How the immune system is able to purge these structures from viral infection with only minimal detrimental effects is still poorly understood. In the present work we studied how an attenuated lymphocytic choriomeningitis virus can be cleared from the central nervous system in the absence of overt disease. We show that elimination of the virus from brain ependyma, but not from brain parenchyma, could be achieved by a T cell-dependent mechanism operating independently of major histocompatibility class I antigens and perforin. Considering that cytotoxic T lymphocyte-mediated cytotoxicity is a leading cause of viral immunopathology and tissue damage, our findings may explain why the most common viral intruders of the central nervous system rarely represent a serious threat to our health.
authors.affiliation: Department of Pathology and Immunology, W.H.O. Collaborating Centre for Neonatal Vaccinology, University of Geneva, Geneva, Switzerland.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer
authors.forename: Mariann
authors.initials: M
authors.lastname: Schedensack
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergthaler
authors.forename: Edit
authors.initials: E
authors.lastname: Horvath
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000821:virology; D004805:Ependyma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D019562:Viral Load / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D054353:Perforin