title: Anti-viral effector T cell responses and trafficking are not dependent upon DRAK2 signaling following viral infection of the central nervous system.
abstract: The signaling events involved in T cell trafficking into the central nervous system (CNS) following viral infection are not fully understood. Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by an immune-mediated demyelinating disease. Although chemokine signaling is critical in promoting T cell infiltration into the CNS and control of viral replication, additional signaling pathways have not been completely explored. DRAK2, a lymphoid-restricted serine/threonine kinase, prevents spurious T cell activation. Yet Drak2- / - mice are resistant to MOG-induced experimental autoimmune encephalomyelitis (EAE), suggesting that DRAK2 may influence T cell trafficking into the CNS. In order to further characterize the molecular mechanisms governing T cell activation and accumulation within the CNS in response to viral infection, MHV was instilled into the CNS of Drak2- / - mice. Drak2-deficient T cells possessed no obvious defects in trafficking into the CNS following MHV infection. Moreover, Drak2-deficient T cell activation, expansion and cytokine production were unimpaired in response to acute MHV infection. These results demonstrate that DRAK2 signaling is dispensable for T cell recruitment into the CNS following viral infection, suggesting that the resistance of Drak2- / - mice to EAE is not due to overt T cell trafficking defects.
authors.affiliation: Center for Immunology and Department of Molecular Biology & Biochemistry, University of California, Irvine, CA, 92697-3900, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Ramos
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Hardison
authors.forename: Linda N
authors.initials: LN
authors.lastname: Stiles
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
authors.forename: Craig M
authors.initials: CM
authors.lastname: Walsh
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology* / Q000821:virology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D006517:Murine hepatitis virus / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C495197:Drak2 protein, mouse; D017346:Protein Serine-Threonine Kinases