title: B7-mediated costimulation of CD4 T cells constrains cytomegalovirus persistence.
abstract: Cytomegalovirus (CMV) utilizes multiple strategies to modulate immunity and promote lifelong, persistent/latent infection, including suppressing T cell activation pathways. Here we examined the role of B7 costimulatory ligands in establishing immune détente from both the host and virus perspectives. Mice lacking both B7.1 and B7.2 showed reduced early expansion of CMV-specific CD4 T cells, consequently allowing for enhanced levels of persistent virus replication. In turn, a CMV mutant lacking expression of the m138 and m147.5 gene products, which restrict B7.1 and B7.2 expression in infected antigen-presenting cells, induced a more robust CD4 T cell response and showed decreased persistence. Together, these data reveal a requirement for B7-mediated signaling in regulating the CMV-specific CD4 T cell response and establishing host-virus equilibrium.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Min J
authors.initials: MJ
authors.lastname: Her
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schneider-Ohrum
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Shellam
authors.forename: Edith
authors.initials: E
authors.lastname: Janssen
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse