title: Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8(+) T-cell priming and viral control.
abstract: Clinically used human vaccination aims to induce specific antibodies that can guarantee long-term protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lymphoid organs is essential for immune activation. In this study we used the lymphocytic choriomeningitis virus (LCMV) to determine whether enforced virus replication occurs in the presence of virus-specific antibodies or virus-specific CD8(+) T cells. We found that after systemic recall infection with LCMV-WE the presence of virus-specific antibodies allowed intracellular replication of virus in the marginal zone of spleen. In contrast, specific antibodies limited viral replication in liver, lung, and kidney. Upon recall infection with the persistent virus strain LCMV-Docile, viral replication in spleen was essential for the priming of CD8(+) T cells and for viral control. In contrast to specific antibodies, memory CD8(+) T cells inhibited viral replication in marginal zone but failed to protect mice from persistent viral infection. We conclude that virus-specific antibodies limit viral infection in peripheral organs but still allow replication of LCMV in the marginal zone, a mechanism that allows immune boosting during recall infection and thereby guarantees control of persistent virus.
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Vishal
authors.initials: V
authors.lastname: Khairnar
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Sarah-Kim
authors.initials: SK
authors.lastname: Friedrich
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.|Department of Cardiothoracic Surgery, Cologne University, Heart Center, Kerpener strasse 62, 50937 Cologne, Germany.
authors.forename: Asmae
authors.initials: A
authors.lastname: Gassa
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Namir
authors.initials: N
authors.lastname: Shaabani
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gailus
authors.affiliation: Department of Hematology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Botezatu
authors.affiliation: Department of Hematology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Khandanpour
authors.affiliation: Institute of Virology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf 40225, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hardt
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf 40225, Germany.|Molecular Medicine II, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf 40225, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.affiliation: Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.|Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf 40225, Germany.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000821:virology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral