title: Production of random classes of immunoglobulins in brain tissue during persistent viral infection paralleled by secretion of interleukin-6 (IL-6) but not IL-4, IL-5, and gamma interferon.
abstract: The activities of cytokines were determined in cerebrospinal fluid (CSF) and serum of mice persistently or intracerebrally acutely infected with lymphocytic choriomeningitis (LCM) virus (LCMV). In contrast to CBA/J (LCMV carrier) mice that responded with low levels of LCMV-specific antibody, high-responder NMRI (carrier) mice showed antibody production by B cells outside of lymphoid organs. The B cells that had infiltrated the brains of LCMV carrier mice exhibited no preferential immunoglobulin isotype or subtype virus-specific antibody production. Phenotypic analysis of the brain infiltrates in virus carrier mice revealed dominance of CD4+ T cells in contrast to virtual absence of CD4+ and dominance of CD8+ in mice with acute LCM. In NMRI but not in CBA/J carrier mice, significant concentrations of interleukin-6 (IL-6) were detected in CSF and serum; IL-2, IL-4, IL-5, granulocyte-macrophage CSF (GM-CSF), and gamma interferon (IFN-gamma) were not elevated. In contrast, during acute, lethal LCM, IL-6 and IFN-gamma were found at high concentrations, and IL-4, IL-5, and GM-CSF were detectable in CSF and serum, but virus-specific antibody-producing cells were not (yet) detectable in the brain. Thus, distinct cytokine patterns are found in acute versus chronic LCMV infection of the brain: in LCM carrier mice, local random-class immunoglobulin production correlated with the absence of IL-2, IL-4, IL-5, and IFN-gamma but active secretion of IL-6.
authors.affiliation: Department of Pathology, University Hospital, Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Moskophidis
authors.forename: K
authors.initials: K
authors.lastname: Frei
authors.forename: J
authors.initials: J
authors.lastname: Löhler
authors.forename: A
authors.initials: A
authors.lastname: Fontana
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation; D001921:Brain / Q000276:immunology* / Q000382:microbiology; D007136:Immunoglobulins / Q000032:analysis*; D007371:Interferon-gamma / Q000032:analysis*; D015847:Interleukin-4 / Q000032:analysis*; D015848:Interleukin-5 / Q000032:analysis*; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D010641:Phenotype; D013045:Species Specificity
chemical_list: D000914:Antibodies, Viral; D007136:Immunoglobulins; D015848:Interleukin-5; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma