title: CD27-CD70 costimulation controls T cell immunity during acute and persistent cytomegalovirus infection.
abstract: Cytomegaloviruses (CMVs) establish lifelong infections that are controlled in part by CD4(+) and CD8(+) T cells. To promote persistence, CMVs utilize multiple strategies to evade host immunity, including modulation of costimulatory molecules on infected antigen-presenting cells. In humans, CMV-specific memory T cells are characterized by the loss of CD27 expression, which suggests a critical role of the costimulatory receptor-ligand pair CD27-CD70 for the development of CMV-specific T cell immunity. In this study, the in vivo role of CD27-CD70 costimulation during mouse CMV infection was examined. During the acute phase of infection, the magnitudes of CMV-specific CD4(+) and CD8(+) T cell responses were decreased in mice with abrogated CD27-CD70 costimulation. Moreover, the accumulation of inflationary memory T cells during the persistent phase of infection and the ability to undergo secondary expansion required CD27-CD70 interactions. The downmodulation of CD27 expression, however, which occurs gradually and exclusively on inflationary memory T cells, is ligand independent. Furthermore, the IL-2 production in both noninflationary and inflationary CMV-specific T cells was dependent on CD27-CD70 costimulation. Collectively, these results highlight the importance of the CD27-CD70 costimulation pathway for the development of CMV-specific T cell immunity during acute and persistent infection.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Suzanne P M
authors.initials: SP
authors.lastname: Welten
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.forename: Kees L
authors.initials: KL
authors.lastname: Franken
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Felix M
authors.initials: FM
authors.lastname: Wensveen
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Klaas P J M
authors.initials: KP
authors.lastname: van Gisbergen
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
mesh_terms: D000208:Acute Disease; D000818:Animals; D053282:CD27 Ligand / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism
chemical_list: D053282:CD27 Ligand; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7