title: The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven inflammation.
abstract: The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell-mediated inflammation. This was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. Mice were infected in the footpad, and the induced CD8(+) T-cell-dependent inflammation was evaluated in mice subjected to treatment with vMIP-II. We found that inflammation was markedly inhibited in mice treated during the efferent phase of the antiviral immune response. In vitro studies revealed that vMIP-II inhibited chemokine-induced migration of activated CD8(+) T cells, but not T-cell-target cell contact, granule exocytosis, or cytokine release. Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were injected directly into the test site. In contrast to the marked inhibition of the effector phase, the presence of vMIP-II during the afferent phase of the immune response did not result in significant suppression of virus-induced inflammation. Taken together, these results indicate that chemokine-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation.
authors.affiliation: Laboratory for Molecular Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Lindow
authors.forename: Anneline
authors.initials: A
authors.lastname: Nansen
authors.forename: Christina
authors.initials: C
authors.lastname: Bartholdy
authors.forename: Annette
authors.initials: A
authors.lastname: Stryhn
authors.forename: Nils J V
authors.initials: NJ
authors.lastname: Hansen
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Boesen
authors.forename: Timothy N C
authors.initials: TN
authors.lastname: Wells
authors.forename: Thue W
authors.initials: TW
authors.lastname: Schwartz
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D018925:Chemokines; C108059:vMIP-II