title: CD40 ligand is pivotal to efficient control of virus replication in mice infected with lymphocytic choriomeningitis virus.
abstract: CD40 ligand (CD40L) is an important molecule that is known to be involved in T-B collaboration and certain aspects of cell-mediated immunity. However, its role in antiviral immunity has not been clearly defined as of yet. Therefore, mice with a targeted defect in the gene encoding this molecule were infected with one of two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in the host. Infection with lymphocytic choriomeningitis virus is initially controlled primarily by CD8+ effector cells, whereas long-term immune surveillance also depends upon CD4+ cells and B cells. Our results reveal that the primary activation, clonal expansion, and differentiation of CD8+ T cells does not require expression of CD40L. However, lack of expression results in rapid impairment of CTL responsiveness and failure to permanently control virus replication. This happens not only in mice infected with the rapidly spreading virus strain but also at a late stage in mice infected with the strain of more limited potential for spreading. In the latter mice, virus replication is initially controlled very efficiently, but high levels of virus can be detected in the blood and internal organs approximately 6 mo after virus inoculation. Since the impairment of immune function seems to be more pronounced in CD40L-deficient mice than in mice lacking either CD4+ cells or B cells, these results indicate that CD40L is pivotal to sustain efficient antiviral immune surveillance, including CD8+ T cells, and suggest that CD40L is critically involved in cellular interactions in addition to T-B cooperation.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark. A.R.Thomsen@sb.immi.ku.dk
authors.forename: A R
authors.initials: AR
authors.lastname: Thomsen
authors.forename: A
authors.initials: A
authors.lastname: Nansen
authors.forename: J P
authors.initials: JP
authors.lastname: Christensen
authors.forename: S O
authors.initials: SO
authors.lastname: Andreasen
authors.forename: O
authors.initials: O
authors.lastname: Marker
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D007157:Immunologic Surveillance; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication
chemical_list: D008562:Membrane Glycoproteins; D023201:CD40 Ligand